Quinazolinone derivative compounds showing anti-cancer activity and the synthesis methods of these compounds

Abstract

The invention relates to quinazolinone-derived compounds that show anticancer activity on the adenocarcinoma human alveolar basal epithelial cell line (A549) by inducing apoptosis in lung cancer cells through inhibition of the epidermal growth factor receptor (EGFR), and at the same time do not have any cytotoxic effects on healthy cells, and to the synthesis methods of these compounds The general structure of the compounds of the invention is shown by Formula (X).

Description

[0001] QUINAZOLINONE DERIVATIVE COMPOUNDS SHOWING ANTI-CANCER ACTIVITY AND THE SYNTHESIS METHODS OF THESE COMPOUNDS

[0002] Technical Field of the Invention

[0003] The invention relates to quinazolinone-derived compounds that show anticancer activity on the adenocarcinoma human alveolar basal epithelial cell line (A549) by inducing apoptosis in lung cancer cells through inhibition of the epidermal growth factor receptor (EGFR), and at the same time do not have any cytotoxic effects on healthy cells, and to the synthesis methods of these compounds.

[0004] State of the Art

[0005] Cancer is a disease characterized by the growth of abnormal cells in the body caused by gene mutation and uncontrolled cell proliferation. In addition to the health problems it brings with it, cancer is a disease that requires long-term struggle both financially and spiritually. Cancer, which affects 18 million people and causes the death of 9.5 million people every year in the world, affects all people regardless of age, gender, language, religion or race. If the similar course of cancer continues, 29.5 million new cases are expected to occur in 2040. While lung cancer is the most common type of cancer among men in the world, it is also ranked 3rdamong women. It is estimated that there were nearly 2 million new cases and 1 .7 million deaths in the world in 2018. Lung cancer is the most common cause of death from cancer worldwide. Lung cancer is when cells from structurally normal lung tissue proliferate unnecessarily and out of control, forming a mass (tumour) within the lung. In other words, the tumour formed by the abnormal and uncontrolled proliferation of lung parenchyma and bronchial tree cells is called lung cancer. The mass / tumour formed here first grows in its environment, and in later stages, it spreads to surrounding tissues or distant organs through circulation (such as liver, bone, brain, etc.) and causes damage. This spread is called metastasis [1].

[0006] In the state of the art, surgery, chemotherapy and radiotherapy methods can be applied alone or together in the treatment of lung cancer. The treatments to be applied vary depending on the stage of the disease. If the disease can be detected at a very early stage, surgical treatment alone may be sufficient. Standard treatment is chemotherapy and radiotherapy in limited stage patients, and chemotherapy alone in extensive stage patients. In the early stages (stages 1 and 2 and some stage 3) the recommended treatment is surgery. Surgery can be performed by removing only a part of the lung lobe (lobectomy, segmentectomy) or the entire lung (pneumonectomy). However, every surgery has a risk, even if small. In addition, approximately 80-85% of lung cancer patients who consult a doctor have lost their chance of being treated with surgery. Therefore, surgery cannot be recommended for every patient. Radiation therapy is used to destroy cancerous cells and shrink the tumour. Curative radiotherapy is applied to early-stage cancer patients in cases where surgical treatment cannot be applied, or in patients where surgery is not medically possible. However, the results are not as good as surgical treatment. In stage III cases undergoing surgical treatment, radiotherapy can be added to the post-surgical treatment. Radiotherapy is used in the treatment of symptoms related to compression and metastases seen in advanced lung cancer. At this stage, radiotherapy is not curative, but symptomatic. Another treatment method, chemotherapy, is to stop the growth and proliferation of the patient's tumour cells. During treatment, along with tumour cells, normal healthy cells are also damaged. These undesirable treatment-related side effects can be listed as nausea, vomiting, diarrhoea, neutropenia, hair loss, kidney and liver dysfunction, skin rashes and sensitivity to sunlight, etc. For reasons such as the fact that every surgery has a risk, albeit small, that radiotherapy, which is a second option in cases where surgical treatment cannot be applied, is not as effective as surgical treatment, and that in chemotherapy, which is a chemical treatment method, normal healthy cells are also damaged along with tumour cells during the treatment, the need for more effective treatment methods that do not require surgery and have reduced side effects is increasing day by day.

[0007] Following traditional treatment methods such as chemotherapy, which began to be widely used in the treatment of lung cancer in the 1990s, innovative and targeted treatments have begun to emerge since 2004. Especially in recent years, with the use of targeted drugs as a treatment model, research into whether these are sufficiently effective in treating different types of diseases has gained momentum. In the classical treatment model, a standard treatment approach is applied according to the histopathological type of cancer. If the chosen treatment method is not compatible with the determined cancer genetic structure, the patient may be exposed to the side effects of the drug during the period in which this drug can affect the cancerous cells, and during this period when it is not treated, the cancer may spread to the body through blood or lymph, causing the patient to die before the expected time. In targeted treatment methods, personalised treatment can be performed according to the gene mutations detected by examining the cancer cell. However, personalised treatment methods are not widely used in the treatment of lung cancer in the world, and therefore it is impossible to say that there is complete success in the targeted treatment approach in the treatment of lung cancer. Rapid epigenetic mutations in treatments with EGFR inhibitors and subsequent resistance to drugs constitute the limitations and inadequacies in this field [2],

[0008] In the state of the art, with the development of the first generation erlotinib and gefitinib, interest in Epidermal growth factor receptor (EGFR) inhibitors developed for the treatment of lung cancer has increased since 2004. Erlotinib and Gefitinib are examples of EGFR tyrosine kinase inhibitors used in the treatment of non-small cell lung cancer. Epidermal growth factor receptor (EGFR), which is part of the ErbB family of tyrosine kinases, is a cell surface receptor that controls the transmission pathways of signals that regulate proliferation and apoptosis in the cell. These transmembrane receptors exist as monomers on the cell surface and are activated when interacting with extracellular signals. EGFR consists of three parts: the part on the cell surface to which the stimulating molecule binds, the cell membrane part, and the part that shows enzyme activity within the cell. When this receptor is activated, it causes signal transmission within the cell and, as a result, intracellular changes. When an abnormality (change, mutation) occurs in the gene encoding EGFR, EGFR works hard, leading to an increase in the growth and proliferation of cancer cells. EGFR mutations are responsible for approximately 10% of nonsmall cell lung cancers (NSCLC). Considering that lung cancer is the most common cancer worldwide, this rate corresponds to approximately 150 thousand new lung cancer cases annually. Although there are some studies in the state of the art that show an inhibition effect on the epidermal growth factor receptor (EGFR), there is no approach to reduce the cytotoxic effects of the derivatives obtained as a result of these studies on healthy cells.

[0009] In the patent document numbered CN1 10903253A, quinazolinone derivatives that have inhibitory activity against EGFR, VEGFR-2 and FGFR1 kinase and anticancer effect on the A549 lung cancer cell line are revealed. However, there is no statement in the patent document that said quinazolinone derivatives do not have any cytotoxic effect on normal / healthy cells at minimum concentration.

[0010] In another study conducted by Malleshappa N.Noolvi et al. , which is within the state of the art, substituted quinazoline and quinoxaline derivatives were synthesised and the in vitro anti-tumour activities of these derivatives were investigated. Although it has been stated that said quinazoline and quinoxaline derivatives show inhibitory activity against EGFR and have anticancer activity on the A549 lung cancer cell line, there is no statement in said article that the said quinazoline and quinoxaline derivatives do not show any cytotoxic effect on normal / healthy cells at minimum concentration [3].

[0011] Resistance to chemotherapy drugs is the most important factor preventing the success of cancer chemotherapy. Continuous use of a single compound increases drug resistance of cancer cells and reduces treatment response. In addition, given that chemotherapy is administered periodically at regular intervals, acquired resistance to the drug in continuous use limits the clinical usefulness of even the most advanced drugs. At this point, new drugs need to be developed.

[0012] Although intensive work is being carried out worldwide to develop new drugs that are available in the state of the art and can have an effect against lung cancer, there are problems such as the serious side effects caused by the drugs in use and the cytotoxic effects of the drugs in question on non-cancerous cells. In addition, due to facts such as the drugs in the state of the art and used in the treatment of lung cancer are insufficient to inhibit the epidermal growth factor receptor (EGFR), which causes an increase in the growth and proliferation of cancer cells, and therefore to induce apoptosis in lung cancer cells, and also cancer cells gain a certain resistance to all drugs used in lung treatment in the state of the art, it has been necessary to develop a new compound that inhibits EGFR, the epidermal growth factor receptor, and thus induces apoptosis in lung cancer cells, and at the same time does not have any cytotoxic effects on healthy cells and, in addition, to which the lung cancer cells cannot yet resist.

[0013] Brief Description and Aims of the Invention

[0014] In the invention, quinazolinone-derived compounds that show anticancer activity on the adenocarcinoma human alveolar basal epithelial cell line by inducing apoptosis in lung cancer cells through inhibition of the epidermal growth factor receptor EGFR, and at the same time do not have any cytotoxic effects on healthy cells, and to the synthesis methods of these compounds.

[0015] The general structure of the compounds of the invention is shown by Formula X.

[0016] Formula X

[0017] An aim of the invention is to introduce new compounds that show anticancer activity on the adenocarcinoma human alveolar basal epithelial cell line (A549) and to which cancerous cells will not show resistance if used. By means of the novelty of the compounds of the invention, the resistance of cancerous cells is eliminated. Continuous use of a single compound increases the drug resistance of cancer cells and makes them more sensitive to the drug and reduces the treatment response. By means of the compounds of the invention, this problem is eliminated.

[0018] Another aim of the invention is to introduce compounds that show anticancer activity on the adenocarcinoma human alveolar basal epithelial cell line (A549), provide inhibition of EGFR, the epidermal growth factor receptor, and at the same time do not have any cytotoxic effects on healthy cells. The fact that the quinazolinone derivative compounds of the invention does not have any cytotoxic effect on healthy cells while they show anticancer activity on the adenocarcinoma human alveolar basal epithelial cell line (A549) and provide inhibition of EGFR, the epidermal growth factor receptor has been proven by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) experiment. In the invention, to determine cytotoxicity, in vitro experiments performed for 24 hours on the non-small cell lung cancer cell line (A549-ATCC® CCL-185™) and the healthy mouse fibroblast cell line (L-929 ATCC® CCL-1 TM) on healthy cells were applied. In these experiments, the tested compounds were applied at different doses to cells provided with suitable living conditions by the MTT (3 -(4,5- dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) method and were stained with MTT. The basis of the method is that the number of viable cells can be calculated by measuring the absorbance of the yellow MTT dye as a result of the reduction of viable cells by the mitochondrial dehydrogenase enzyme and their transformation into purple formazan crystals. According to the determined result, while the tested compounds caused deterioration and death when applied at low concentrations on lung cancer cells, this occurred at relatively higher concentrations in the healthy cell line, so it was determined that they were not selective, that is, cytotoxic, on healthy cells. Another aim of the invention is to provide compounds that inhibit EGFR, the epidermal growth factor receptor. With the inhibition of EGFR, the epidermal growth factor receptor, apoptosis in lung cancer cells is induced and anticancer activity is provided on the adenocarcinoma human alveolar basal epithelial cell line (A549). The fact that the quinazolinone derivative compounds of the invention provide inhibition of EGFR, the epidermal growth factor receptor, has been proven by in vitro enzyme experiments performed on the compounds. To determine EGFR tyrosine kinase inhibition, the EGFR kinase assay kit (BPS Bioscience, Catalogue no 40321 , San Diego, CA, USA) was used according to the manufacturer's instructions. Four independent experiments were performed for each compound and the mean standard deviation was calculated. Gefitinib was used as a positive control. The purpose of targeting EGFR inhibition is to inhibit EGFR by causing conformational changes on the protein by molecules binding to various active pockets of EGFR overexpressed in the cancerous cell and by preventing the EGF substrate from binding to the EGFR receptor. Thus, it shows anticancer activity by making cell death a healthy process as a result of inducing apoptotic mechanisms in the cell. Molecular docking and molecular dynamics simulation studies have been conducted to understand anticancer mechanisms at the molecular level. Caspase-3 (PDB ID: 4QTX) and EGFR (PDB ID: 2ITY) X-ray crystal structures were downloaded from the Protein Data Bank server (www.pdb.org, accessed 01 August 2019). Schrodinger Suite 2020 protocols were applied to map protein structures, ligands, and protein active site. The pH values of both the protein and the compounds were prepared in accordance with the environment of 7.4±1.0. Finally, the exposures obtained by applying the standard precision placement method (SP) for placement processes were evaluated. Then, the best exposure of the most active compound was determined and molecular dynamics simulations were carried out for ligand -protein complexes for 100 ns at 31 OK temperature by adding water, 0.15M NaCI and membrane cholesterols according to Schrodinger Suite 2020 protocols.

[0019] Description of Drawings

[0020] Figure 1.1H-NMR spectrum of A / -(4-Chlorophenyl)-2-{2-[4-oxoquinazolin-3(4 / - / )-yl]acetyl}hydrazine-1 - carbotioamide compound (Compound 1 )

[0021] Figure 2.13C-NMR spectrum of A / -(4-Chlorophenyl)-2-{2-[4-oxoquinazolin-3(4 / - / )-yl]acetyl}hydrazine-1 - carbotioamide compound (Compound 1 )

[0022] Figure 3. HRMS spectrum of A / -(4-Chlorophenyl)-2-{2-[4-oxoquinazolin-3(4 / - / )-yl]acetyl}hydrazine-1 - carbotioamide compound (Compound 1 )

[0023] Figure 4.1H-NMR spectrum of A / -(3-Chlorophenyl)-2-{2-[4-oxoquinazolin-3(4 / - / )-yl]acetyl}hydrazine-1 - carbotioamide compound (Compound 2)

[0024] Figure 5.13C-NMR spectrum of A / -(3-Chlorophenyl)-2-{2-[4-oxoquinazolin-3(4 / - / )-yl]acetyl}hydrazine-1 - carbotioamide compound (Compound 2)

[0025] Figure 6. HRMS spectrum of A / -(3-Chlorophenyl)-2-{2-[4-oxoquinazolin-3(4 / - / )-yl]acetyl}hydrazine-1 - carbotioamide compound (Compound 2) Figure 7.1H-NMR spectrum of / V-6-Chlorobenzothiazol-2-yl)-2-[(4-(4-methoxyphenyl)-5-{[4- oxoquinazolin-3(4 / 4)-yl]methyl}-4 / 7-1 ,2,4-triazole-3-yl)thio]acetamide compound (Compound 3)

[0026] Figure 8.13C-NMR spectrum of / V-6-Chlorobenzothiazol-2-yl)-2-[(4-(4-methoxyphenyl)-5-{[4- oxoquinazolin-3(4 / 4)-yl]methyl}-4 / 7-1 ,2,4-triazole-3-yl)thio]acetamide compound (Compound 3)

[0027] Figure 9. HRMS spectrum of / V-6-Chlorobenzothiazol-2-yl)-2-[(4-(4-methoxyphenyl)-5-{[4- oxoquinazolin-3(4 / 4)-yl]methyl}-4 / 7-1 ,2,4-triazole-3-yl)thio]acetamide compound (Compound 3)

[0028] Figure 10.1H-NMR spectrum of A / -(Benzothiazol-2-yl)-2-[(4-(4-methoxyphenyl)-5-{[4-oxoquinazolin- 3(4 / 4)-yl]methyl}-4 / 7-1 ,2,4-triazole-3-yl)thio]acetamide compound (Compound 4)

[0029] Figure 11.13C-NMR spectrum of A / -(Benzothiazol-2-yl)-2-[(4-(4-methoxyphenyl)-5-{[4-oxoquinazolin- 3(4 / 4)-yl]methyl}-4 / 7-1 ,2,4-triazole-3-yl)thio]acetamide compound (Compound 4)

[0030] Figure 12. HRMS spectrum of A / -(Benzothiazol-2-yl)-2-[(4-(4-methoxyphenyl)-5-{[4-oxoquinazolin- 3(4 / 4)-yl]methyl}-4 / 7-1 ,2,4-triazole-3-yl)thio]acetamide compound (Compound 4)

[0031] Figure 13.1H-NMR spectrum of A / -6-Methylbenzothiazol-2-yl)-2-[(4-(4-methoxyphenyl)-5-{[4- oxoquinazolin-3(4 / 4)-yl]methyl}-4 / 7-1 ,2,4-triazole-3-yl)thio]acetamide compound (Compound 5)

[0032] Figure 14.13C-NMR spectrum of A / -6-Methylbenzothiazol-2-yl)-2-[(4-(4-methoxyphenyl)-5-{[4- oxoquinazolin-3(4 / 4)-yl]methyl}-4 / 7-1 ,2,4-triazole-3-yl)thio]acetamide compound (Compound 5)

[0033] Figure 15. HRMS spectrum of A / -6-Methylbenzothiazol-2-yl)-2-[(4-(4-methoxyphenyl)-5-{[4- oxoquinazolin-3(4 / 4)-yl]methyl}-4 / 7-1 ,2,4-triazole-3-yl)thio]acetamide compound (Compound 5)

[0034] Figure 16.1H-NMR spectrum of A / -6-Fluorobenzothiazol-2-yl)-2-[(4-(4-amino)-5-{[4-oxoquinazolin- 3(4 / 4)-yl]methyl}-4 / 7-1 ,2,4-triazole-3-yl)thio]acetamide compound (Compound 6)

[0035] Figure 17.13C-NMR spectrum of A / -6-Fluorobenzothiazol-2-yl)-2-[(4-(4-amino)-5-{[4-oxoquinazolin- 3(4 / 4)-yl]methyl}-4 / 7-1 ,2,4-triazole-3-yl)thio]acetamide compound (Compound 6)

[0036] Figure 18. HRMS spectrum of A / -6-Fluorobenzothiazol-2-yl)-2-[(4-(4-amino)-5-{[4-oxoquinazolin-3(4 / - / )- yl]methyl}-4 / 7-1 ,2,4-triazole-3-yl)thio]acetamide compound (Compound 6)

[0037] Figure 19.1H-NMR spectrum of A / -(6-Chlorobenzothiazol-2-yl)-2-[(4-(4-amino)-5-{[4-oxoquinazolin- 3(4 / 4)-yl]methyl}-4 / 7-1 ,2,4-triazole-3-yl)thio]acetamide compound (Compound 7)

[0038] Figure 20.13C-NMR spectrum of A / -(6-Chlorobenzothiazol-2-yl)-2-[(4-(4-amino)-5-{[4-oxoquinazolin- 3(4 / 4)-yl]methyl}-4 / 7-1 ,2,4-triazole-3-yl)thio]acetamide compound (Compound 7)

[0039] Figure 21. HRMS spectrum of A / -(6-Chlorobenzothiazol-2-yl)-2-[(4-(4-amino)-5-{[4-oxoquinazolin- 3(4 / 4)-yl]methyl}-4 / 7-1 ,2,4-triazole-3-yl)thio]acetamide compound (Compound 7)

[0040] Figure 22.1H-NMR spectrum of A / -(Benzothiazol-2-yl)-2-[(4-(4-amino)-5-{[4-oxoquinazolin-3(4 / - / )- yl]methyl}-4 / 7-1 ,2,4-triazole-3-yl)thio]acetamide compound (Compound 8) Figure 23.13C-NMR spectrum of (Benzothiazol-2-yl)-2-[(4-(4-amino)-5-{[4-oxoquinazolin-3(4 / 7)- yl]methyl}-4 / 7-1 ,2,4-triazole-3-yl)thio]acetamide compound (Compound 8)

[0041] Figure 24. HRMS spectrum of A / -(Benzothiazol-2-yl)-2-[(4-(4-amino)-5-{[4-oxoquinazolin-3(4 / - / )- yl]methyl}-4 / 7-1 ,2,4-triazole-3-yl)thio]acetamide compound (Compound 8)

[0042] Figure 25. Quadrants of the apoptosis results of active compounds and controls

[0043] Figure 26. Quadrants of caspase-3 activation results of active compounds and controls

[0044] Figure 27. Quadrants of mitochondrial depolarisation results of active compounds and controls

[0045] Figure 28. Docking study on caspase-3 enzyme (PDBID: 4QTX)

[0046] Figure 29. MDS study on Caspase-3 enzyme (Compound 6-Caspase-3 enzyme complex)

[0047] Figure 30. Docking study on EGFR protein (PDBID: 2ITY)

[0048] Figure 31 . MDS study of compound 6-EGFR complex

[0049] Detailed Description of the Invention

[0050] The invention relates to quinazolinone-derived compounds that show anticancer activity on the adenocarcinoma human alveolar basal epithelial cell line (A549) by inducing apoptosis in lung cancer cells through inhibition of the epidermal growth factor receptor EGFR, and at the same time do not have any cytotoxic effects on healthy cells, and to the synthesis methods of these compounds. The general structure of the compounds of the invention is shown by Formula X.

[0051] Formula X

[0052] Compounds that are the subject of the invention are

[0053] • A / -(4-Chlorophenyl)-2-{2-[4-oxoquinazolin-3(4 / - / )-yl]acetyl}hydrazine-1 -carbotioamide (Compound 1 ) • A / -(3-Chlorophenyl)-2-{2-[4-oxoquinazolin-3(4 / 7)-yl]acetyl}hydrazine-1 -carbotioamide (Compound 2)

[0054] • A / -6-Chlorobenzothiazol-2-yl)-2-[(4-(4-methoxyphenyl)-5-{[4-oxoquinazolin-3(4 / 7)-yl]methyl}- 4 / 7-1 ,2,4-triazole-3-yl)thio]acetamide (Compound 3)

[0055] • A / -(Benzothiazol-2-yl)-2-[(4-(4-methoxyphenyl)-5-{[4-oxoquinazolin-3(4 / 7)-yl]methyl}-4 / 7-1 ,2,4- triazole-3-yl)thio]acetamide (Compound 4)

[0056] • A / -6-Methylbenzothiazol-2-yl)-2-[(4-(4-methoxyphenyl)-5-{[4-oxoquinazolin-3(4 / 7)-yl]methyl}- 4 / 7-1 ,2,4-triazole-3-yl)thio]acetamide (Compound 5)

[0057] • A / -6-Florobenzothiazol-2-yl)-2-[(4-(4-amino)-5-{[4-oxoquinazolin-3(4 / 7)-yl]methyl}-4 / 7-1 ,2,4- triazole-3-yl)thio]acetamide (Compound 6)

[0058] • A / -6-Chlorobenzothiazol-2-yl)-2-[(4-(4-amino)-5-{[4-oxoquinazolin-3(4 / 7)-yl]methyl}-4 / 7-1 ,2,4- triazole-3-yl)thio]acetamide (Compound 7)

[0059] • A / -(Benzothiazol-2-yl)-2-[(4-(4-amino)-5-{[4-oxoquinazolin-3(4 / 7)-yl]methyl}-4 / 7-1 ,2,4-triazole-3- yl)thio]acetamide (Compound 8)

[0060] Said compounds show anticancer activity on the adenocarcinoma human alveolar basal epithelial cell line (A549) by inducing apoptosis in lung cancer cells by inhibiting EGFR, the epidermal growth factor receptor, and at the same time, they do not have any cytotoxic effects on healthy cells.

[0061] Formula X wherein R is selected from the formulas below:

[0062]

[0063] R7 Ra In said Formula X, the A / -(4-Chlorophenyl)-2-{2-[4-oxoquinazolin-3(4 / - / )-yl]acetyl}hydrazine-1 - carbotioamide compound obtained when R group is R=Ri is indicated by Formula 1 .

[0064] Formula 1

[0065] It is a white powder and its melting temperature is in the range of 243-244°C.1H-NMR (300 MHz, DMSO-cfe): 5 4.79 (s, 2H, N-CH2), 7.43 (d, J= 8.72 Hz, 2H, phenyl H3,s), 7.55-7.61 (m, 3H, phenyl H2,6 and quinazoline He), 7.73 (d, J= 7.76 Hz, H, quinazoline He), 7.87 (td, 4i=1 .52 Hz, 42=7.65 Hz, H, quinazoline H7), 8.16 (dd, 4i=1 .21 Hz, 42=7.99 Hz, H, quinazoline Hs), 8.34 (s, H, quinazoline H2), 9.54 (brs, H, CO-NH-NH-CS-NH), 9.93 (brs, H, CO-NH-NH-CS-NH), 10.60 (brs, H, CS- NH-phenyl).13C-NMR (75 MHz, DMSO-de): 47.86 (N-CH2), 121 .82, 126.45, 127.30, 127.77, 128.61 , 135.15, 138.41 , 148.49, 148.74, 161 .06, 167.25 (C=O), 181 .02 (C=S).

[0066] HRMS (-m / z): [M+H]+: for C17H14N5O2SCI, calculated: 388.0629, found: 388.0643. In said Formula X, the A / -(3-Chlorophenyl)-2-{2-[4-oxoquinazolin-3(4 / - / )-yl]acetyl}hydrazine-1 - carbotioamide compound obtained when R group is R=R2 is indicated by Formula 2 .

[0067] Formula 2 It is a white powder and its melting temperature is in the range of 243-244°C.

[0068] 1H-NMR (300 MHz, DMSO-cfe): 5 4.80 (s, 2H, N-CH2), 7.24 (d, J= 7.31 Hz, H, phenyl H4), 7.40 (t, 4=8.03 Hz, H, phenyl Hs), 7.56-7.61 (m, 2H, phenyl He and quinazoline He), 7.72-7.75 (m, 2H, phenyl H2 and quinazoline He), 7.87 (td, J / =1 .48 Hz, J2=7.67 Hz, H, quinazoline H7), 8.16 (dd, J / =1 .16 Hz, J2=7.97 Hz, H, quinazoline H5), 8.36 (s, H, quinazoline H2), 9.54 (brs, H, CO-NH-NH-CS-NH), 10.02 (brs, H, CO- NH-NH-CS-NH), 10.64 (brs, H, CS-NH-phenyl).

[0069] 13C-NMR (75 MHz, DMSO-cfe): 47.99, 121 .80, 123.79, 124.82, 125.31 , 126.38, 127.79, 130.32, 132.76, 135.18, 140.93 148.51 , 148.70, 161 .13, 167.26, 170.92 (C=O), 180.87 (C=S).

[0070] HRMS (-m / z): [M+H]+: for C17H14N5O2SCI, calculated: 388.0629, found: 388.0636.

[0071] In said Formula X, the A / -(6-Chlorobenzothiazol-2-yl)-2-[(4-(4-methoxyphenyl)-5-{[4-oxoquinazolin- 3(4 / - / )-yl]methyl}-4 / 7-1 ,2,4-triazol-3-yl)thio]acetamide compound obtained when R group is R= R3 is indicated by Formula 3 .

[0072] Formula 3 It is a white powder and its melting temperature is in the range of 274-275°C.

[0073] 1H-NMR (300 MHz, DMSO-cfe): 5 3.83 (s, 3H, OCH3), 3.95 (s, 2H, S-CH2), 5.16 (s, 2H, N-CH2), 7.1 1 - 7.18 (m, 3H, phenyl Hs.sand benzothiazole Hs) 7.34 (d, 4=8.56 Hz, H, benzothiazole H7), 7.48 (d, 4=8.79 Hz, 2H, phenyl H2,e), 7.56 (t, J=7.55 Hz, H, quinazoline He), 7.67-7.71 (m, 2H, quinazoline He and benzothiazole H4), 7.86 (t, 4=7.91 Hz, H, quinazoline H7), 8.1 1 (d, 4=7.90 Hz, H, quinazoline Hs), 8.36 (s, H, quinazoline H2).

[0074] 13C-NMR (75 MHz, DMSO-cfe): 40.82 (S-CH2), 41 .12 (N-CH2), 56.04 (OCH3), 1 1 5.57, 119.83, 120.48, 120.51 , 121 .88, 124.47, 124.74, 125.36, 126.50, 127.71 , 128.95, 135.09, 148.32, 149.89, 151 .62, 153.38, 160.26, 160.67, 169.43, 172.31 (C=O).

[0075] HRMS (-m / z): [M+H]+: for C27H20N7O3S2CI calculated: 590.0830; found: 590.0824.

[0076] In said Formula X, the A / -(Benzothiazol-2-yl)-2-[(4-(4-methoxyphenyl)-5-{[4-oxoquinazolin-3(4 / - / )- yl]methyl}-4 / 7-1 ,2,4-triazol-3-yl)thio]acetamide compound obtained when R group is R= R4 is indicated by Formula 4 .

[0077] Formula 4

[0078] It is a powder with an off-white appearance and its melting temperature is in the range of 243-244°C.

[0079] 1H-NMR (300 MHz, DMSO-cfe): 5 3.82 (s, 3H, OCH3), 4.07 (s, 2H, S-CH2), 5.16 (s, 2H, N-CH2), 7.08- 7.14 (m, 3H, phenyl Hs.s and benzothiazole Hs), 7.26 (td, Ji= 1 .12, J2= 7.61 Hz, H, benzothiazole H4), 7.48 (d, J= 8.78 Hz, 2H, phenyl H2,e), 7.50-7.58 (m, 2H, quinazoline Heand benzothiazole Hs), 7.69-7.76 (m, 2H, quinazoline Hs and benzothiazole H7), 7.85 (td, Ji= 1 .44 Hz, J2= 7.63 Hz, H, quinazoline H7), 8.09 (dd, Ji= 1 .10 Hz, J 2= 8.14 Hz, H, quinazoline Hs), 8.36 (s, H, quinazoline H2).

[0080] 13C-NMR (75 MHz, DMSO-cfe): 40.75 (S-CH2), 41 .13 (N-CH2), 56.04 (O-CH2), 1 15.58, 1 19.74, 121 .49, 121 .86, 122.00, 125.20, 125.37, 126.50, 127.7137, 128.93, 132.79, 135.08, 148.30, 150.19, 151 .90, 152.67, 160.26, 160.72, 164.73, 170.16 (C=O). HRMS (-m / z): [M+H]+: for C27H21 N7O3S2, calculated: 556.1203, found: 556.1220.

[0081] In said Formula X, the A / -(6-Methylbenzothiazole-2-yl)-2-[(4-(4-methoxyphenyl)-5-{[4-oxoquinazolin- 3(4 / - / )-yl]methyl}-4 / 7-1 ,2,4-triazol-3-yl)thio]acetamide compound obtained when R group is R= Rs is indicated by Formula 5.

[0082] Formula 5

[0083] It is a powder with an off-white appearance and its melting temperature is in the range of 254-255°C.

[0084] 1H-NMR (300 MHz, DMSO-cfe): 5 2.35 (s, 3H, CH3), 3.82 (s, 3H, OCH3), 4.05 (s, 2H, S-CH2), 5.16 (s, 2H, N-CH2), 7.07 (dd, J / =1.00 Hz, J2=8.29 Hz, benzothiazole Hs), 7.12 (d, J=8.91 Hz, 2H, phenyl H3,s), 7.40 (d, J=8.15 Hz, H, benzothiazole H7), 7.48 (d, J=8.88 Hz, 2H, phenyl H2,6), 7.53-7.58 (m, 2H, quinazoline He and benzothiazole H4), 7.70 (d, J=7.96 Hz, H, quinazoline Hs), 7.85 (td, J / =1 .36 Hz, J2=7.67 Hz, H, quinazoline H7), 8.10 (dd, J / =0.99 Hz, J2=7.8O Hz, H, quinazoline Hs), 8.36 (s, H, quinazoline H2).

[0085] 13C-NMR (75 MHz, DMSO-cfe): 21 .44 (CH3), 40.75 (S-CH2), 41 .14 (N-CH2), 56.04 (O-CH3), 1 15.58, 1 19.43, 121 .30, 121 .86, 125.20, 126.49, 126.65, 127.71 , 128.92, 131 .14, 132.93, 135.08, 148.07, 148.30, 151 .89, 152.70, 160.26, 160.71 , 163.97, 169.92 (C=O).

[0086] HRMS (-m / z): [M+H]+: for C28H23N7O3S2 calculated: 570.1377, found: 570.1368.

[0087] In said Formula X, the A / -(6-Fluorobenzothiazole-2-yl)-2-[(4-(4-amino)-5-{[4-oxoquinazolin-3(4 / - / )- yl]methyl}-4 / 7-1 ,2,4-triazol-3-yl)thio]acetamide compound obtained when R group is R=Re is indicated by Formula 6.

[0088]

[0089] Formula 6

[0090] It is a light brown powder and its melting temperature is in the range of 239-240°C.

[0091] 1H-NMR (300 MHz, DMSO-cfe): 4.07 (s, 2H, S-CH2), 5.35 (s, 2H, N-CH2), 6.27 (brs, 2H, N-NH2), 7.14 (td, Ji=2.70 Hz, 4^9.1 1 Hz, H, benzothiazole Hs), 7.53-7.60 (m, 2H, benzothiazole H7 and quinazoline He), 7.66-7.71 (m, 2H, quinazoline He and benzothiazole H4), 7.84 (td, 4;=1 .49 Hz, 42=7.67 Hz, H, quinazoline H7), 8.14 (dd, 4 / =1 .19 HZ, 42=7.95 Hz, H, quinazoline Hs), 8.47 (s, H, quinazoline H2).

[0092] 13C-NMR (75 MHz, DMSO-cfe): 38.14 (S-CH2), 40.29 (N-CH2), 107.81 ve 108.13, 1 13.29 ve 1 13.61 , 120.77, 120.89, 121 .96, 126.57, 127.70, 133.70, 133.84, 135.05, 146.60, 148.33, 152.53, 153.00, 156.82, 159.97 ve 160.56, 163.83, 170.52 (C=O).

[0093] HRMS (-m / z): [M+H]+: for C20H15N8O2S2F calculated: 483.0816, found: 483.0819.

[0094] In said Formula X, the A / -(6-Chlorobenzothiazole-2-yl)-2-[(4-(4-amino)-5-{[4-oxoquinazolin-3(4 / - / )- yl]methyl}-4 / 7-1 ,2,4-triazol-3-yl)thio]acetamide compound obtained when R group is R=R? is indicated by Formula 7.

[0095] Formula 7

[0096] It is a brown powder and its melting temperature is in the range of 208-209°C.

[0097] 1H-NMR (300 MHz, DMSO-cfe): 5 3.89 (s, 2H, S-CH2), 5.34 (s, 2H, N-CH2), 6.31 (brs, 2H, N-NH2), 7.20

[0098] (dd, 4?=1 .95 Hz, 4 =8.59 Hz, H, benzothiazole Hs), 7.43 (d, 4= 8.53 Hz, H, quinazoline He), 7.56 (t, 4= 7.57 Hz, H, quinazoline He), 7-70-7.73 (m, 2H, benzothiazole H? and benzothiazole H4), 7.85 (t, J=7.65 Hz, H, quinazoline H7), 8.15 (d, J=7.96 Hz, H, quinazoline Hs), 8.47 (s, H, quinazoline H2).

[0099] 13C-NMR (75 MHz, DMSO-cfe): 40.59 (S-CH2), 120.16, 120.63, 121 .97, 124.89, 125.01 , 126.03, 126.58, 127.70, 134.94, 135.07, 148.33, 148.50, 149.61 , 152.30, 153.38, 160.53, 168.83, 172.86 (C=O).

[0100] HRMS (-m / z): [M+H]+: for C20H15N8O2S2CI, calculated: 499.0521 , found: 499.0526.

[0101] In said Formula X, the A / -(6-Benzothiazole-2-yl)-2-[(4-(4-amino)-5-{[4-oxoquinazolin-3(4 / 4)-yl]methyl}- 4 / 7-1 ,2,4-triazol-3-yl)thio]acetamide compound obtained when R group is R=Rs is indicated by Formula 8.

[0102] Formula 8

[0103] It is a light brown powder and its melting temperature is in the range of 221 -222°C.

[0104] 1H-NMR (300 MHz, DMSO-cfe): 5 3.91 (s, 2H, S-CH2), 5.36 (s, 2H, N-CH2), 6.35 (brs, 2H, N-NH2), 7.03 (td, Ji= 0.97 Hz, J2= 7 A7 Hz, H, benzothiazole Hs), 7.21 (td, Ji= 1 .16, J2= 7.6 Hz, H, benzothiazole H4), 7.47 (d, J= 7.97 Hz, H, benzothiazole Hs), 7.56 (td, Ji= 1 .10 Hz, Jz= 7.53 Hz, H, quinazoline He), 7.65- 7.73 (m, 2H, quinazoline He and benzothiazole H7), 7.87 (td, Ji= 1 .55 Hz, J2= 7.99 Hz, H, quinazoline H7), 8.15 (dd, Ji= 1 .26 Hz, J2= 7.96 Hz, H, quinazoline Hs), 8.49 (s, H, quinazoline H2).

[0105] 13C-NMR (75 MHz, DMSO-cfe): 39.47 (S-CH2), 40.64 (N-CH2), 1 19.23, 121 .22, 121 .99, 124.89, 126.58, 127.71 , 133.18, 135.06, 148.36, 148.52, 150.69, 152.32, 153.43, 157.44, 160.44, 160.54, 168.05, 172.34 (C=O).

[0106] HRMS (-m / z): [M+H]+: for C20H16N8O2S2 calculated: 465.0910, found: 465.0910.

[0107] Synthesis method of compounds (Compound 1 -2) that show anticancer activity on adenocarcinoma human alveolar basal epithelial cell line (A549) by inducing apoptosis in lung cancer cells by inhibition of EGFR, the epidermal growth factor receptor, are of the quinazolinone derivative compounds that do not have any cytotoxic effects on healthy cells and are shown with Formula 1 -2, comprises the process steps of: i. mixing anthranilic acid with a mol of formamide equivalent to 1 .2 times the anthranilic acid used in the oil bath, and controlling the reaction in this process by thin layer chromatography (TLC), and then terminating the reaction by pouring the reaction mixture into ice water; afterwards, washing the precipitated part with water, filtering and drying, and crystallising the dried precipitated part from hexane after drying to obtain 4-quinazolinone or by reacting anthranilic acid with a mol of formamide equivalent to 1 .2 times the anthranilic acid used in the microwave and controlling the reaction in this process with TLC, and then terminating the reaction by pouring the reaction mixture into ice water; then, obtaining 4-quinazolinone by washing the precipitated part with water, filtering, drying and crystallizing the dried precipitated part from hexane, ii. dissolving 4-quinazolinone in acetone and adding 1 .5 times the mole of potassium carbonate (K2CO3) to the reaction flask as 4-quinazolinone used; then, adding 1 .1 times mol of 4-quinazolinone and ethyl 2-bromoacetate to the mixture, reacting the mixture with a reversing cooling apparatus and completing the reaction with TLC, and after the end of the reaction, evaporating the acetone from the mixture and washing the precipitated part with water and filtering it to obtain ethyl 2-[4-oxoquinazolin-3(4 / - / )-yl]acetate,

[0108] Hi. dissolving ethyl 2-[4-oxoquinazolin-3(4 / - / )-yl]acetate in ethanol and adding 1.5 times mol of hydrazine monohydrate / ethanol solution as ethyl 2-[4-oxoquinazolin-3(4 / - / )-yl]acetate to the solution portion by portion and keeping the resulting mixture at room temperature overnight, then, completing the reaction with TLC and separating the precipitated part by filtration and drying, then, crystallising the dried precipitated part with ethanol and obtaining 2-[4- oxoquinazolin-3(4 / - / )-yl]acetohydrazide, iv. adding 4-chlorophenylisothiocyanate or 3-chlorophenylisothiocyanate, one of the alkyl / aryl isothiocyanate derivatives dissolved in alcohol, in equal moles to the 2-[4-oxoquinazolin- 3(4 / - / )-yl]acetohydrazide compound dissolved in ethanol in an ice bath and controlling the reaction with TLC; then, washing the precipitated part with alcohol, filtering and drying, and after recrystallising the dried precipitate from alcohol, obtaining A / -(4-Chlorophenyl)-2-{2-[4- oxoquinazolin-3(4 / - / )-yl]acetyl}hydrazine-1 -carbotioamide compound (Compound 1 ) or the A / -(3-Chlorophenyl)-2-{2-[4-oxoquinazolin-3(4 / - / )-yl]acetyl}hydrazine-1 -carbotioamide compound (Compound 2).

[0109] In case 4-chlorophenylisothiocyanate is used as the alkyl / aryl isothiocyanate derivative in the process step (iv), A / -(4-Chlorophenyl)-2-{2-[4-oxoquinazolin-3(4 / - / )-yl]acetyl}hydrazine-1 -carbotioamide compound (Compound 1 ) is synthesised and in case 3-chlorophenylisothiocyanate is used as the alkyl / aryl isothiocyanate derivative in the process step (iv), A / -(3-Chlorophenyl)-2-{2-[4-oxoquinazolin- 3(4 / - / )-yl]acetyl}hydrazine-1 -carbotioamide compound (Compound 2) is synthesised.

[0110] In a different embodiment of the invention, the synthesis method of compounds (Compound 1 -2) that show anticancer activity on adenocarcinoma human alveolar basal epithelial cell line (A549) by inducing apoptosis in lung cancer cells by inhibition of EGFR, the epidermal growth factor receptor, are of the quinazolinone derivative compounds that do not have any cytotoxic effects on healthy cells and are shown with Formula 1 -2, comprises the process steps of: i. mixing 27.428 g, 0.2 mol anthranilic acid with a mol of formamide equivalent to 1 .2 times the anthranilic acid used in the oil bath for 4-8 hours, and controlling the reaction in this process by thin layer chromatography (TLC), and then terminating the reaction by pouring the reaction mixture into ice water; afterwards, washing the precipitated part with water, filtering and drying, and crystallising the dried precipitated part from hexane after drying to obtain 4-quinazolinone or by reacting 27.428 g, 0.2 mol anthranilic acid with a mol of formamide equivalent to 1 .2 times the anthranilic acid used in the microwave at 500 W for 10-20 minutes and controlling the reaction in this process with TLC, and then terminating the reaction by pouring the reaction mixture into ice water; then, obtaining 4-quinazolinone by washing the precipitated part with water, filtering, drying and crystallizing the dried precipitated part from hexane, ii. dissolving 40 g, 274 mmol 4-quinazolinone in acetone and adding 1.5 times the mole of potassium carbonate (K2CO3) to the reaction flask as 4-quinazolinone used; then, adding 1 .1 times mol of 4-quinazolinone and ethyl 2-bromoacetate to the mixture, reacting the mixture with a reversing cooling apparatus and completing the reaction with TLC, and after the end of the reaction, evaporating the acetone from the mixture and washing the precipitated part with water and filtering it to obtain ethyl 2-[4-oxoquinazolin-3(4 / - / )- yl]acetate,

[0111] Hi. dissolving 46 g, 198 mmol ethyl 2-[4-oxoquinazolin-3(4 / - / )-yl]acetate in ethanol and adding 1 .5 times mol of hydrazine monohydrate / ethanol solution as 2-[4-oxoquinazolin-3(4 / - / )- yl]acetate to the solution portion by portion and keeping the resulting mixture at room temperature overnight, then, completing the reaction with TLC and separating the precipitated part by filtration and drying, then, crystallising the dried precipitated part with ethanol and obtaining 2-[4-oxoquinazolin-3(4 / - / )-yl]acetohydrazide, iv. adding 4-chlorophenylisothiocyanate or 3-chlorophenylisothiocyanate, one of the alkyl / aryl isothiocyanate derivatives dissolved in alcohol, in equal moles to the 20 g, 92 mmol 2-[4- oxoquinazolin-3(4 / - / )-yl]acetohydrazide compound dissolved in ethanol in an ice bath and controlling the reaction with TLC; then, washing the precipitated part with alcohol, filtering and drying, and after recrystallising the dried precipitate from alcohol, obtaining A / -(4- Chlorophenyl)-2-{2-[4-oxoquinazolin-3(4 / - / )-yl]acetyl}hydrazine-1 -carbotioamide compound (Compound 1 ) or the A / -(3-Chlorophenyl)-2-{2-[4-oxoquinazolin-3(4 / - / )-yl]acetyl}hydrazine- 1 -carbotioamide compound (Compound 2).

[0112] In a different embodiment of the invention, the synthesis method of compounds (Compound 1 -2) that show anticancer activity on adenocarcinoma human alveolar basal epithelial cell line (A549) by inducing apoptosis in lung cancer cells by inhibition of EGFR, the epidermal growth factor receptor, are of the quinazolinone derivative compounds that do not have any cytotoxic effects on healthy cells and are shown with Formula 1 -2, comprises the process steps of: i. mixing 27.428 g, 0.2 mol anthranilic acid with a mol of formamide equivalent to 1 .2 times the anthranilic acid used in the oil bath for 6 hours, and controlling the reaction in this process by thin layer chromatography (TLC), and then terminating the reaction by pouring the reaction mixture into ice water; afterwards, washing the precipitated part with water, filtering and drying, and crystallising the dried precipitated part from hexane after drying to obtain 4-quinazolinone or by reacting 27.428 g, 0.2 mol anthranilic acid with a mol of formamide equivalent to 1 .2 times the anthranilic acid used in the microwave at 500 W for 15 minutes and controlling the reaction in this process with TLC, and then terminating the reaction by pouring the reaction mixture into ice water; then, obtaining 4-quinazolinone by washing the precipitated part with water, filtering, drying and crystallizing the dried precipitated part from hexane, ii. dissolving 40 g, 274 mmol 4-quinazolinone in acetone and adding 1.5 times the mole of potassium carbonate (K2CO3) to the reaction flask as 4-quinazolinone used; then, adding 1 .1 times mol of 4-quinazolinone and ethyl 2-bromoacetate to the mixture, reacting the mixture with a reversing cooling apparatus and completing the reaction with TLC, and after the end of the reaction, evaporating the acetone from the mixture and washing the precipitated part with water and filtering it to obtain ethyl 2-[4-oxoquinazolin-3(4 / - / )- yl]acetate,

[0113] Hi. dissolving 46 g, 198 mmol ethyl 2-[4-oxoquinazolin-3(4 / - / )-yl]acetate in ethanol and adding 1 .5 times mol of hydrazine monohydrate / ethanol solution as ethyl 2-[4-oxoquinazolin-3(4 / - / )- yl]acetate to the solution portion by portion and keeping the resulting mixture at room temperature overnight, then, completing the reaction with TLC and separating the precipitated part by filtration and drying, then, crystallising the dried precipitated part with ethanol and obtaining 2-[4-oxoquinazolin-3(4 / - / )-yl]acetohydrazide, iv. adding 4-chlorophenylisothiocyanate or 3-chlorophenylisothiocyanate, one of the alkyl / aryl isothiocyanate derivatives dissolved in alcohol, in equal moles to the 20 g, 92 mmol 2-[4- oxoquinazolin-3(4 / - / )-yl]acetohydrazide compound dissolved in ethanol in an ice bath and controlling the reaction with TLC; then, washing the precipitated part with alcohol, filtering and drying, and after recrystallising the dried precipitate from alcohol, obtaining A / -(4- Chlorophenyl)-2-{2-[4-oxoquinazolin-3(4 / - / )-yl]acetyl}hydrazine-1 -carbotioamide compound (Compound 1 ) or the A / -(3-Chlorophenyl)-2-{2-[4-oxoquinazolin-3(4 / - / )-yl]acetyl}hydrazine- 1 -carbotioamide compound (Compound 2).

[0114] Synthesis method of compounds (Compound 3-8) that show anticancer activity on adenocarcinoma human alveolar basal epithelial cell line (A549) by inducing apoptosis in lung cancer cells by inhibition of EGFR, the epidermal growth factor receptor, are of the quinazolinone derivative compounds that do not have any cytotoxic effects on healthy cells and are shown with Formula 3-8, comprises the process steps of: i. mixing anthranilic acid with a mol of formamide equivalent to 1 .2 times the anthranilic acid used in the oil bath, and controlling the reaction in this process by thin layer chromatography (TLC), and then terminating the reaction by pouring the reaction mixture into ice water; afterwards, washing the precipitated part with water, filtering and drying, and crystallising the dried precipitated part from hexane after drying to obtain 4-quinazolinone or by reacting anthranilic acid with a mol of formamide equivalent to 1 .2 times the anthranilic acid used in the microwave and controlling the reaction in this process with TLC, and then terminating the reaction by pouring the reaction mixture into ice water; then, obtaining 4-quinazolinone by washing the precipitated part with water, filtering, drying and crystallizing the dried precipitated part from hexane, ii. dissolving 4-quinazolinone in acetone and adding 1 .5 times the mole of potassium carbonate (K2CO3) to the reaction flask as 4-quinazolinone used; then, adding 1 .1 times mol of 4-quinazolinone and ethyl 2-bromoacetate to the mixture, reacting the mixture with a reversing cooling apparatus and completing the reaction with TLC, and after the end of the reaction, evaporating the acetone from the mixture and washing the precipitated part with water and filtering it to obtain ethyl 2-[4-oxoquinazolin-3(4 / - / )-yl]acetate, iii. dissolving ethyl 2-[4-oxoquinazolin-3(4 / - / )-yl]acetate in ethanol and adding 1.5 times mol of hydrazine monohydrate / ethanol solution as 2-[4-oxoquinazolin-3(4 / - / )-yl]acetate to the solution portion by portion and keeping the resulting mixture at room temperature overnight, then, completing the reaction with TLC and separating the precipitated part by filtration and drying, then, crystallising the dried precipitated part with ethanol and obtaining 2-[4- oxoquinazolin-3(4 / - / )-yl]acetohydrazide, iv. adding equal moles of 4-methoxyphenylisothiocyanate dissolved in alcohol onto the 2-[4- oxoquinazolin-3(4 / - / )-yl]acetohydrazide compound dissolved in ethanol in an ice bath and controlling the reaction with TLC; then, washing the precipitated part with alcohol, filtering and drying. and obtaining A / -(4-Methoxyphenyl)-2-{2-[4-oxoquinazolin-3(4 / - / )- yl]acetyl}hydrazine-1 -carbotioamide after recrystallising the dried precipitate from alcohol, v. boiling the A / -(4-Methoxyphenyl)-2-{2-[4-oxoquinazolin-3(4 / - / )-yl]acetyl}hydrazine-1 - carbotioamide and sodium hydroxide (NaOH) in ethanol solution with reflux apparatus and finishing the reaction with TLC; after the end of the reaction, pouring the mixture into ice water and adjusting the pH of the mixture to 7 with dilute hydrochloric acid (HCI) solution, then, filtering the precipitated part and washing with water, then crystallising the precipitated part from ethanol to obtain compound 3-{[4-(4-Methoxyphenyl)-5-thioxo-4,5-dihydro-1 H- 1 ,2,4-triazol-3-yl]methyl}quinazolin-4(3 / )-on, vi. dissolving 2-[4-Oxoquinazolin-3(4 / - / )-yl]acetohydrazide and sodium hydroxide (NaOH) in ethanol solution and adding 1 .2 times the amount of carbon disulphide (CS2) to the resulting mixture in an ice bath and keeping the resulting mixture in an ice bath and then at room temperature and boiling the mixture under reflux after precipitations are observed in the mixture; then, the completing reaction with TLC, after the reaction is completed, pouring the mixture into ice water and adjusting the pH of the mixture to 7 with dilute hydrochloric acid (HCI) solution; then, filtering the precipitated part and washing with water, and then crystallising the precipitated part is from ethanol and obtaining the 3-[(5-Thioxo-4,5-dihydro-

[0115] 1 .3.4-oxadiazol-2-yl)methyl]quinazolin-4(3 / - / )-on compound, vii. dissolving the 3-[(5-Thioxo-4,5-dihydro-1 ,3,4-oxadiazol-2-yl)methyl]quinazolin-4(3 / - / )-on compound in ethanol and adding 2 times the mol of 3-[(5-Thioxo-4,5-dihydro-1 ,3,4- oxadiazol-2-yl)methyl]quinazolin-4(3 / - / )-one to hydrazine monohydrate and boiling the resulting mixture; then completing the reaction with TLC, and after the reaction is completed, washing the precipitated part with ethanol and filtering and crystallizing the precipitated part from alcohol to obtain the 3-[(4-Amino-5-thioxo-4,5-dihydro-1 H-1 ,2,4- triazol-3-yl)methyl)quinazolin-4(3 / - / )-on compound, viii. mixing the obtained 3-{[4-(4-Methoxyphenyl)-5-thioxo-4,5-dihydro-1 H-1 ,2,4-triazol-3- yl]methyl}quinazolin-4(3 / - / )-on and 3-[(4-Amino-5-thioxo-4,5-dihydro-1 H-1 ,2,4-triazol-3- yl)methyl)quinazolin-4(3 / - / )-on compounds with 3-{[4-(4-Methoxyphenyl)-5-thioxo-4,5- dihydro-1 H-1 ,2,4-triazol-3-yl]methyl}quinazolin-4(3 / 7)-on and 1 times mole of N-(6- chlorobenzothiazol-2-yl)-2-chloroacetamide, N-(benzothiazol-2-yl)-2-chloroacetamide or N- (6-methylbenzothiazol-2-yl)-2-chloroacetamide derivatives among the 2-chloro-A / -aryl acetamide derivatives of 3-{[4-(4-Methoxyphenyl)-5-thioxo-4,5-dihydro- / / 7-1 ,2,4-triazol-3- yl]methyl}quinazolin-4(3 / - / )-on substance and with 3-[(4-Amino-5-thioxo-4,5-dihydro-1 H-

[0116] 1 .2.4-triazol-3-yl)methyl)quinazolin-4(3 / - / )-on and 1 times mole of N-(6-fluorobenzothiazol- 2-yl)-2-chloroacetamide, A / -(6-chlorobenzothiazol-2-yl)-2-chloroacetamide or N- (benzothiazol-2-yl)-2-chloroacetamide derivatives among 2-chloro-A / -aryl acetamide derivatives of 3-[(4-Amino-5-thioxo-4,5-dihydro-1 H-1 ,2,4-triazol-3-yl)methyl)quinazolin- 4(3 / - / )-on substance in acetone at room temperature under the catalyst of potassium carbonate (K2CO3) 1 .5 times the molar amount of mercapto derivative; after the end of the reaction, evaporating the solvent in the mixture and washing the solid part is with water and filtering, and then crystallizing the dried solid part from ethanol and synthesising A / -(4- Chlorophenyl)-2-{2-[4-oxoquinazolin-3(4 / - / )-yl]acetyl}hydrazine-1 -carbotioamide (Compound 1 ), A / -(3-Chlorophenyl)-2-{2-[4-oxoquinazolin-3(4 / - / )-yl]acetyl}hydrazine-1 - carbotioamide (Compound 2), A / -6-Chlorobenzothiazol-2-yl)-2-[(4-(4-methoxyphenyl)-5-{[4- oxoquinazolin-3(4 / - / )-yl]methyl}-4 / 7-1 ,2,4-triazole-3-yl)thio]acetamide (Compound 3), N- (Benzothiazol-2-yl)-2-[(4-(4-methoxyphenyl)-5-{[4-oxoquinazolin-3(4 / - / )-yl]methyl}-4 / 7-

[0117] 1 .2.4-triazole-3-yl)thio]acetamide (Compound 4), A / -6-Methylbenzothiazol-2-yl)-2-[(4-(4- methoxyphenyl)-5-{[4-oxoquinazolin-3(4 / - / )-yl]methyl}-4 / 7-1 ,2,4-triazole-3-yl)thio]acetamide (Compound 5), A / -6-Florobenzothiazol-2-yl)-2-[(4-(4-amino)-5-{[4-oxoquinazolin-3(4 / - / )- yl]methyl}-4 / 7-1 ,2,4-triazole-3-yl)thio]acetamide (Compound 6), A / -6-Chlorobenzothiazol-2- yl)-2-[(4-(4-amino)-5-{[4-oxoquinazolin-3(4 / 4)-yl]methyl}-4 / 7-1 ,2,4-triazole-3- yl)thio]acetamide (Compound 7) or A / -(Benzothiazol-2-yl)-2-[(4-(4-amino)-5-{[4- oxoquinazolin-3(4 / 4)-yl]methyl}-4 / 7-1 ,2,4-triazole-3-yl)thio]acetamide (Compound 8).

[0118] In case 2-chloro-N-(6-chlorobenzothiazol-2-yl)acetamide is used as 2-chloro-N-aryl acetamide derivative in process step (viii) A / -(6-Chlorobenzothiazol-2-yl)-2-[(4-(4-methoxyphenyl)-5-{[4- oxoquinazolin-3(4 / 4)-yl]methyl}-4 / 7-1 ,2,4- triazol-3-yl)thio]acetamide compound (Compound 3) is synthesised; in case 2-chloro-N-(benzothiazol-2-yl)acetamide is used as 2-chloro-N-aryl acetamide derivative in process step (viii), A / -(Benzothiazol-2-yl)-2-[(4-(4-methoxyphenyl)-5-{[4-oxoquinazolin- 3(4 / 4)-yl]methyl}-4 / 7-1 ,2,4-triazole- 3-yl)thio]acetamide compound (Compound 4) is synthesised; in case 2-chloro-N-(6-methylbenzothiazol-2-yl)acetamide is used as 2-chloro-N-aryl acetamide derivative in process step (viii), A / -(6-Methylbenzothiazol-2-yl)-2-[(4-(4-methoxyphenyl)-5-{[4-oxoquinazolin-3(4 / 4)- yl]methyl}-4 / 7-1 ,2,4- triazol-3-yl)thio]acetamide compound (Compound 5) is synthesised; in case 2- chloro-N-(6-fluorobenzothiazol-2-yl)acetamide is used as 2-chloro-N-aryl acetamide derivative in process step (viii), A / -(6-Fluorobenzothiazol-2-yl)-2-[(4-(4-amino)-5-{[4-oxoquinazolin-3(4 / 4)-yl]methyl}- 4 / 7-1 ,2,4- triazol-3-yl)thio]acetamide compound (Compound 6) is synthesised; in case 2-chloro-N-(6- chlorobenzothiazol-2-yl)acetamide is used as 2-chloro-N-aryl acetamide derivative in process step (viii), A / -(6-Chlorobenzothiazol-2-yl)-2-[(4-(4-amino)-5-{[4-oxoquinazolin-3(4 / 4)-yl]methyl}-4 / 7-1 ,2,4- triazol-3- yl)thio]acetamide compound (Compound 7) is synthesised; and in case 2-chloro-N-(benzothiazol-2- yl)acetamide is used as the 2-chloro-N-aryl acetamide derivative in process step (viii), A / -(Benzothiazol- 2-yl)-2-[(4-(4-amino)-5-{[4-oxoquinazolin-3(4 / 4)-yl]methyl}-4 / 7-1 ,2,4-triazole- 3-yl)thio]acetamide compound (Compound 8) is synthesised.

[0119] In a different embodiment of the invention, the synthesis method of compounds (Compound 3-8) that show anticancer activity on adenocarcinoma human alveolar basal epithelial cell line (A549) by inducing apoptosis in lung cancer cells by inhibition of EGFR, the epidermal growth factor receptor, are of the quinazolinone derivative compounds that do not have any cytotoxic effects on healthy cells and are shown with Formula 3-8, comprises the process steps of: i. mixing 27.428 g, 0.2 mol anthranilic acid with a mol of formamide equivalent to 1 .2 times the anthranilic acid used in the oil bath for 4-8 hours, and controlling the reaction in this process by thin layer chromatography (TLC), and then terminating the reaction by pouring the reaction mixture into ice water; afterwards, washing the precipitated part with water, filtering and drying, and crystallising the dried precipitated part from hexane after drying to obtain 4-quinazolinone or by reacting 27.428 g, 0.2 mol anthranilic acid with a mol of formamide equivalent to 1 .2 times the anthranilic acid used in the microwave at 500 W for 10-20 minutes and controlling the reaction in this process with TLC, and then terminating the reaction by pouring the reaction mixture into ice water; then, obtaining 4-quinazolinone by washing the precipitated part with water, filtering, drying and crystallizing the dried precipitated part from hexane, ii. adding 1 .5 times the mole of potassium carbonate (K2CO3) to the reaction flask as 4- quinazolinone used; then, adding 1 .1 times mol of 4-quinazolinone and ethyl 2- bromoacetate to the mixture, reacting the mixture with a reversing cooling apparatus and completing the reaction with TLC, and after the end of the reaction, evaporating the acetone from the mixture and washing the precipitated part with water and filtering it to obtain ethyl 2-[4-oxoquinazolin-3(4 / - / )-yl]acetate,

[0120] Hi. dissolving 46 g, 198 mmol ethyl 2-[4-oxoquinazolin-3(4 / - / )-yl]acetate in ethanol and adding 1 .5 times mol of hydrazine monohydrate / ethanol solution as 2-[4-oxoquinazolin-3(4 / - / )- yl]acetate to the solution portion by portion and keeping the resulting mixture at room temperature overnight, then, completing the reaction with TLC and separating the precipitated part by filtration and drying, then, crystallising the dried precipitated part with ethanol and obtaining 2-[4-oxoquinazolin-3(4 / - / )-yl]acetohydrazide, iv. adding equal moles of 4-methoxyphenylisothiocyanate dissolved in alcohol onto the 20 g, 92 mmol 2-[4-oxoquinazolin-3(4 / - / )-yl]acetohydrazide compound dissolved in ethanol in an ice bath and controlling the reaction with TLC; then, washing the precipitated part with alcohol, filtering and drying, and obtaining A / -(4-Methoxyphenyl)-2-{2-[4-oxoquinazolin- 3(4 / - / )-yl]acetyl}hydrazine-1 -carbotioamide after recrystallising the dried precipitate from alcohol, v. boiling the 30g, 78 mmol A / -(4-Methoxyphenyl)-2-{2-[4-oxoquinazolin-3(4 / - / )- yl]acetyl}hydrazine-1 -carbotioamide and 2M sodium hydroxide (NaOH) in ethanol solution with reflux apparatus for 1 -6 hours and finishing the reaction with TLC; after the end of the reaction, pouring the mixture into ice water and adjusting the pH of the mixture to 7 with dilute hydrochloric acid (HCI) solution, then, filtering the precipitated part and washing with water, then crystallising the precipitated part from ethanol to obtain compound 3-{[4-(4- Methoxyphenyl)-5-thioxo-4,5-dihydro-1 H-1 ,2,4-triazol-3-yl]methyl}quinazolin-4(3 / )-on, vi. dissolving 20 g, 92 mmol 2-[4-Oxoquinazolin-3(4 / - / )-yl]acetohydrazide and sodium hydroxide (NaOH) in ethanol solution and adding 1 .2 times the amount of carbon disulphide (CS2) to the resulting mixture in an ice bath and keeping the resulting mixture in an ice bath for 30 minutes and then at room temperature for 10-60 minutes and boiling the mixture under reflux for 2 hours after precipitations are observed in the mixture; then , the completing reaction with TLC, after the reaction is completed, pouring the mixture into ice water and adjusting the pH of the mixture to 7 with dilute hydrochloric acid (HCI) solution; then, filtering the precipitated part and washing with water, and then crystallising the precipitated part is from ethanol and obtaining the 3-[(5-Thioxo-4,5-dihydro-1 ,3,4-oxadiazol-2- yl)methyl]quinazolin-4(3 / - / )-on compound, vii. dissolving the 17 g, 65 mmol 3-[(5-Thioxo-4,5-dihydro-1 ,3,4-oxadiazol-2- yl)methyl]quinazolin-4(3 / - / )-on compound in ethanol and adding 2 times the mol of 3-[(5- Thioxo-4,5-dihydro-1 ,3,4-oxadiazol-2-yl)methyl]quinazolin-4(3 / - / )-one to hydrazine monohydrate and boiling the resulting mixture; then completing the reaction with TLC, and after the reaction is completed, washing the precipitated part with ethanol and filtering and crystallizing the precipitated part from alcohol to obtain the 3-[(4-Amino-5-thioxo-4,5- dihydro-1 H-1 ,2,4-triazol-3-yl)methyl)quinazolin-4(3 / - / )-on compound, viii. mixing the obtained 3-{[4-(4-Methoxyphenyl)-5-thioxo-4,5-dihydro- 7 / 7-1 ,2,4-triazol-3- yl]methyl}quinazolin-4(3 / 7)-on and 3-[(4-Amino-5-thioxo-4,5-dihydro- 7 / 7-1 ,2,4-triazol-3- yl)methyl)quinazolin-4(3H3 / 7 on compounds with 0.3 g, 0.82 mmol 3-{[4-(4- Methoxyphenyl)-5-thioxo-4,5-dihydro- IH- ,2,4-triazol-3-yl]methyl}quinazolin-4(3 / 7)-on and 1 times mole of A / -(6-chlorobenzothiazol-2-yl)-2-chloroacetamide, A / -(benzothiazol-2-yl)-2- chloroacetamide or A / -(6-methylbenzothiazol-2-yl)-2-chloroacetamide derivatives among the 2-chloro-A / -aryl acetamide derivatives of 3-{[4-(4-Methoxyphenyl)-5-thioxo-4,5-dihydro- 7 / 7-1 ,2,4-triazol-3-yl]methyl}quinazolin-4(3 / 7)-on substance and with 0.3 g, 1 mmol 3-[(4- amino-5-thioxo-4,5-dihydro- 7 / 7-1 ,2,4-triazol-3-yl)methyl)quinazolin-4(3H)-on and 1 times mole of A / -(6-fluorobenzothiazol-2-yl)-2-chloroacetamide, A / -(6-chlorobenzothiazol-2-yl)-2- chloroacetamide or A / -(benzothiazol-2-yl)-2-chloroacetamide derivatives among 2-chloro- / V- aryl acetamide derivatives of 3-[(4-amino-5-thioxo-4,5-dihydro- 7 / 7-1 ,2,4-triazol-3- yl)methyl)quinazolin-4(3 / 7)-on substance in acetone at room temperature for 2-6 hours under the catalyst of potassium carbonate (K2CO3) 1 .5 times the molar amount of mercapto derivative; after the end of the reaction, evaporating the solvent in the mixture and washing the solid part is with water and filtering, and then crystallizing the dried solid part from ethanol and synthesising A / -(4-Chlorophenyl)-2-{2-[4-oxoquinazolin-3(4 / 7)- yl]acetyl}hydrazine-1 -carbotioamide (Compound 1 ), N-(3-Chlorophenyl)-2-{2-[4- oxoquinazolin-3(4 / 7)-yl]acetyl}hydrazine-1 -carbotioamide (Compound 2), N-6-

[0121] Chlorobenzothiazol-2-yl)-2-[(4-(4-methoxyphenyl)-5-{[4-oxoquinazolin-3(4 / 7)-yl]methyl}- 4 / 7-1 ,2,4-triazole-3-yl)thio]acetamide (Compound 3), N-(Benzothiazol-2-yl)-2-[(4-(4- methoxyphenyl)-5-{[4-oxoquinazolin-3(4 / 7)-yl]methyl}-4 / 7-1 ,2,4-triazole-3-yl)thio]acetamide (Compound 4), A / -6-Methylbenzothiazol-2-yl)-2-[(4-(4-methoxyphenyl)-5-{[4-oxoquinazolin- 3(4 / 7)-yl]methyl}-4 / 7-1 ,2,4-triazole-3-yl)thio]acetamide (Compound 5), A / -6-

[0122] Florobenzothiazol-2-yl)-2-[(4-(4-amino)-5-{[4-oxoquinazolin-3(4 / 7)-yl]methyl}-4 / 7-1 ,2,4- triazole-3-yl)thio]acetamide (Compound 6), A / -6-Chlorobenzothiazol-2-yl)-2-[(4-(4-amino)- 5-{[4-oxoquinazolin-3(4 / 7)-yl]methyl}-4 / 7-1 ,2,4-triazole-3-yl)thio]acetamide (Compound 7) or A / -(Benzothiazol-2-yl)-2-[(4-(4-amino)-5-{[4-oxoquinazolin-3(4 / 7)-yl]methyl}-4 / 7-1 ,2,4- triazole-3-yl)thio]acetamide (Compound 8).

[0123] In a different embodiment of the invention, the synthesis method of compounds (Compound 3-8) that show anticancer activity on adenocarcinoma human alveolar basal epithelial cell line (A549) by inducing apoptosis in lung cancer cells by inhibition of EGFR, the epidermal growth factor receptor, are of the quinazolinone derivative compounds that do not have any cytotoxic effects on healthy cells and are shown with Formula 3-8, comprises the process steps of: i. mixing 27.428 g, 0.2 mol anthranilic acid with a mol of formamide equivalent to 1 .2 times the anthranilic acid used in the oil bath for 6 hours, and controlling the reaction in this process by thin layer chromatography (TLC), and then terminating the reaction by pouring the reaction mixture into ice water; afterwards, washing the precipitated part with water, filtering and drying, and crystallising the dried precipitated part from hexane after drying to obtain 4-quinazolinone or by reacting 27.428 g, 0.2 mol anthranilic acid with a mol of formamide equivalent to 1 .2 times the anthranilic acid used in the microwave at 500 W for 15 minutes and controlling the reaction in this process with TLC, and then terminating the reaction by pouring the reaction mixture into ice water; then, obtaining 4-quinazolinone by washing the precipitated part with water, filtering, drying and crystallizing the dried precipitated part from hexane, ii. dissolving 40 g, 274 mmol 4-quinazolinone in acetone and adding 1.5 times the mole of potassium carbonate (K2CO3) to the reaction flask as 4-quinazolinone used; then, adding 1 .1 times mol of 4-quinazolinone and ethyl 2-bromoacetate to the mixture, reacting the mixture with a reversing cooling apparatus and completing the reaction with TLC, and after the end of the reaction, evaporating the acetone from the mixture and washing the precipitated part with water and filtering it to obtain ethyl 2-[4-oxoquinazolin-3(4 / 4)- yl]acetate,

[0124] Hi. dissolving 46 g, 198 mmol ethyl 2-[4-oxoquinazolin-3(4 / 4)-yl]acetate in ethanol and adding 1 .5 times mol of hydrazine monohydrate / ethanol solution as 2-[4-oxoquinazolin-3(4 / 4)- yl]acetate to the solution portion by portion and keeping the resulting mixture at room temperature overnight, then, completing the reaction with TLC and separating the precipitated part by filtration and drying, then, crystallising the dried precipitated part with ethanol and obtaining 2-[4-oxoquinazolin-3(4 / 4)-yl]acetohydrazide, iv. adding equal moles of 4-methoxyphenylisothiocyanate dissolved in alcohol onto the 20 g, 92 mmol 2-[4-oxoquinazolin-3(4 / 4)-yl]acetohydrazide compound dissolved in ethanol in an ice bath and controlling the reaction with TLC; then, washing the precipitated part with alcohol, filtering and drying, and obtaining A / -(4-Methoxyphenyl)-2-{2-[4-oxoquinazolin- 3(4 / 4)-yl]acetyl}hydrazine-1 -carbotioamide after recrystallising the dried precipitate from alcohol, v. boiling the 30g, 78 mmol A / -(4-Methoxyphenyl)-2-{2-[4-oxoquinazolin-3(4 / 4)- yl]acetyl}hydrazine-1 -carbotioamide and 2M sodium hydroxide (NaOH) in ethanol solution with reflux apparatus for 2 hours and finishing the reaction with TLC; after the end of the reaction, pouring the mixture into ice water and adjusting the pH of the mixture to 7 with dilute hydrochloric acid (HCI) solution, then, filtering the precipitated part and washing with water, then crystallising the precipitated part from ethanol to obtain compound 3-{[4-(4- Methoxyphenyl)-5-thioxo-4,5-dihydro- 7 / 7-1 ,2,4-triazol-3-yl]methyl}quinazolin-4(3 / 4)-on, vi. dissolving 20 g, 92 mmol 2-[4-Oxoquinazolin-3(4 / 4)-yl]acetohydrazide and sodium hydroxide (NaOH) in ethanol solution and adding 1 .2 times the amount of carbon disulphide (CS2) to the resulting mixture in an ice bath and keeping the resulting mixture in an ice bath for 30 minutes and then at room temperature for 30 minutes and boiling the mixture under reflux for 2 hours after precipitations are observed in the mixture; then, the completing reaction with TLC, after the reaction is completed, pouring the mixture into ice water and adjusting the pH of the mixture to 7 with dilute hydrochloric acid (HCI) solution; then, filtering the precipitated part and washing with water, and then crystallising the precipitated part is from ethanol and obtaining the 3-[(5-Thioxo-4,5-dihydro-1 ,3,4-oxadiazol-2- yl)methyl]quinazolin-4(3 / 7)-on compound, vii. dissolving the 17 g, 65 mmol 3-[(5-Thioxo-4,5-dihydro-1 ,3,4-oxadiazol-2- yl)methyl]quinazolin-4(3 / 7)-on compound in ethanol and adding 2 times the mol of 3-[(5- Thioxo-4,5-dihydro-1 ,3,4-oxadiazol-2-yl)methyl]quinazolin-4(3H)-one to hydrazine monohydrate and boiling the resulting mixture; then completing the reaction with TLC, and after the reaction is completed, washing the precipitated part with ethanol and filte ring and crystallizing the precipitated part from alcohol to obtain the 3-[(4-Amino-5-thioxo-4,5- dihydro-1 H-1 ,2,4-triazol-3-yl)methyl)quinazolin-4(3 / 7)-on compound, viii. mixing the obtained 3-{[4-(4-Methoxyphenyl)-5-thioxo-4,5-dihydro-1 H-1 ,2,4-triazol-3- yl]methyl}quinazolin-4(3 / 7)-on and 3-[(4-Amino-5-thioxo-4,5-dihydro-1 H-1 ,2,4-triazol-3- yl)methyl)quinazolin-4(3 / 7)-on compounds with 0.3 g, 0.82 mmol 3-{[4-(4-Methoxyphenyl)- 5-thioxo-4,5-dihydro- 7 / 7-1 ,2,4-triazol-3-yl]methyl}quinazolin-4(3H)-on and 1 times mole of A / -(6-chlorobenzothiazol-2-yl)-2 -chloroacetamide, A / -(benzothiazol-2-yl)-2 -chloroacetamide or A / -(6-methylbenzothiazol-2-yl)-2-chloroacetamide derivatives among the 2-chloro-N-aryl acetamide derivatives of 3-{[4-(4-Methoxyphenyl)-5-thioxo-4,5-dihydro- 7 / 7-1 ,2,4-triazol-3- yl]methyl}quinazolin-4(3 / 7)-on substance and with 0.3 g, 1 mmol 3-[(4-Amino-5-thioxo-4,5- dihydro- 7 / 7-1 ,2,4-triazol-3-yl)methyl)quinazolin-4(3 / 7)-on and 1 times mole of A / -(6- fluorobenzothiazol-2-yl)-2 -chloroacetamide, A / -(6-chlorobenzothiazol-2-yl)-2- chloroacetamide or A / -(benzothiazol-2-yl)-2-chloroacetamide derivatives among 2-chloro- / V- aryl acetamide derivatives of 3-[(4-Amino-5-thioxo-4,5-dihydro- 7 / 7-1 ,2,4-triazol-3- yl)methyl)quinazolin-4(3 / 7)-on substance in acetone at room temperature for 2 hours under the catalyst of potassium carbonate (K2CO3) 1 .5 times the molar amount of mercapto derivative; after the end of the reaction, evaporating the solvent in the mixture and washing the solid part is with water and filtering, and then crystallizing the dried solid part from ethanol and synthesising A / -(4-Chlorophenyl)-2-{2-[4-oxoquinazolin-3(4 / 7)- yl]acetyl}hydrazine-1 -carbotioamide (Compound 1 ), A / -(3-Chlorophenyl)-2-{2-[4- oxoquinazolin-3(4 / 7)-yl]acetyl}hydrazine-1 -carbotioamide (Compound 2), A / -6-

[0125] Chlorobenzothiazol-2-yl)-2-[(4-(4-methoxyphenyl)-5-{[4-oxoquinazolin-3(4 / 7)-yl]methyl}- 4 / 7-1 ,2,4-triazole-3-yl)thio]acetamide (Compound 3), A / -(Benzothiazol-2-yl)-2-[(4-(4- methoxyphenyl)-5-{[4-oxoquinazolin-3(4 / 7)-yl]methyl}-4 / 7-1 ,2,4-triazole-3-yl)thio]acetamide (Compound 4), A / -6-Methylbenzothiazol-2-yl)-2-[(4-(4-methoxyphenyl)-5-{[4-oxoquinazolin- 3(4 / 7)-yl]methyl}-4 / 7-1 ,2,4-triazole-3-yl)thio]acetamide (Compound 5), A / -6-

[0126] Florobenzothiazol-2-yl)-2-[(4-(4-amino)-5-{[4-oxoquinazolin-3(4 / 7)-yl]methyl}-4 / 7-1 ,2,4- triazole-3-yl)thio]acetamide (Compound 6), A / -6-Chlorobenzothiazol-2-yl)-2-[(4-(4-amino)- 5-{[4-oxoquinazolin-3(4 / 7)-yl]methyl}-4 / 7-1 ,2,4-triazole-3-yl)thio]acetamide (Compound 7) or A / -(Benzothiazol-2-yl)-2-[(4-(4-amino)-5-{[4-oxoquinazolin-3(4 / 7)-yl]methyl}-4 / 7-1 ,2,4- triazole-3-yl)thio]acetamide (Compound 8). Evaluation of cytotoxicity results

[0127] The cytotoxic effects of the compounds that are the subject of the invention were calculated in terms of ICso (pM) as a result of experiments conducted in vitro for 24 hours. The results are also shown in Table 1 . The ICso value calculated for cisplatin, used as the standard drug, was found to be 27.33±6.81 pM. Accordingly, among the compounds that have anticancer activity but do not have a cytotoxic effect on the healthy cell line or have very low activity, the compounds that are more active than cisplatin or show a similar ICso value, in order of activity are listed as Compound 4, Compound 2, Compound 3, Compound 1 , Compound 6, Compound 7, Compound 5 and Compound 8.

[0128] Table 1 . IC50 (pM) doses of the compounds that are the subject of the invention acting on cancer and healthy cell lines.

[0129] A549: Non-small cell lung cancer cell line, L929: Healthy mouse fibroblast cell line, SD: Standard deviation (±) and SI: Selectivity index (Healthy cell ICso value / Cancer cell ICso value). All values were calculated after 24-hour incubation, thus they are 24-hour cytotoxicity values. is used to indicate that no calculation is made.

[0130] Determination of apoptotic activities

[0131] Annexin quadrants and percentage results of the apoptosis tests are shown in Table 1 . While the total early and late apoptotic effects of cisplatin, which was used as a standard drug for positive control, was 22.61 %; the total apoptotic effects for Compounds 1 -8 were 31 .08%, 15.66%, 77.68%, 8.59%, 6.66%, 23.95%, 15.17% and 14.03%, respectively (Compound 1 -8). Accordingly, Compound 3, which has the highest apoptotic effect, has approximately 3.5 times higher apoptotic effect than cisplatin. Compound 1 induces apoptosis with a profile similar to cisplatin.

[0132] Table 1 . Apoptosis results of the compounds that are the subject of the invention

[0133] Q1 : Necrotic cells, Q2: Late apoptotic cells, Q3: Viable cells, Q4: Early apoptotic cells, Q2+Q4: Early and late apoptotic cells. A549 cell line was used in the experiment.

[0134] Evaluation of activity pathways

[0135] After determining the apoptotic activity, the role of caspase activity in observing the apoptosis -inducing effect was investigated. As is known, type-1 programmed cell death, that is, apoptosis, occurs by activating two main pathways, which are intrinsic and extrinsic pathways. In the intracellular pathway (intrinsic pathway), also known as the mitochondrial pathway, a chain of events is initiated by a death signal such as the inability of the mitochondria to carry out glycolysis with ATP. Cytochrome C is released and the apoptosome forms, forming a new form with caspase-9. This new complex structure activates the effector caspase, caspase-3. In the extracellular pathway (extrinsic pathway), caspase-8 is active through death receptors on the membrane surface and activates caspase-3. With the stimulation of caspase-3, type-1 cell death occurs. For this reason, activation of caspase-3 is one of the intersection points of both intrinsic and extrinsic pathways in the induction of apoptosis.

[0136] Evaluation of caspase-3 activation results

[0137] The % positive and % negative activity values of caspase-3 activation results are shown in Table 3 and quadrants in Figure 26. The experiment was performed under in vitro conditions against A549 cells and evaluated after a 24-hour incubation time. Accordingly, the caspase-3 activation value of cisplatin was found to be 34.39%. Enzyme activation of the compounds that are the subject of the invention are, from most effective to least effective, Compound 6, Compound 3, Compound 7, Compound 8, Compound 5, Compound 4, Compound 1 and Compound 2. In this case, the activation percentage of Compound 1 , Compound 2, Compound 4, and Compound 5 was found to be quite ineffective. On the other hand, the activities of Compound 6, Compound 3 and Compound 7 are comparable to cisplatin. In this case, it can be said that the greater effectiveness of compounds containing halogen (chlorine for Compound 3 and Compound 7; fluorine atoms for Compound 6) is related to their lipophilicity properties, and as lipophilicity increases, caspase-3 activation increases. Table 2. Caspase-3% results of active compounds

[0138] Evaluation of mitochondrial membrane depolarisation

[0139] The plots of the results of the mitochondrial membrane depolarisation test are shown in Figure 27 and the percentage values are shown in Table 4. Mitochondrial membrane depolarisation value of cisplatin was calculated as 36.01 %. The effectiveness of synthesised Compound 1 (15.41 %), Compound 2 (14.48%) and Compound 5 (28.96%) was found to be lower than cisplatin. On the other hand, Compound 3 (75.30%) caused mitochondrial dysfunction by providing membrane depolarisation 2.09 times more than cisplatin, Compound 4 (61 .62%) 1 .71 times, Compound 6 (96.13%) 2.67 times, Compound 7 (83.70%) 2.32 times, and Compound 8 (75.30%) 2.09 times. Although there are various mechanisms that may cause mitochondrial membrane depolarisation, the reason for observing a situation like this study is thought to be the disruption of mitochondrial dynamics as a result of growth factor inhibition, especially in non-small cell lung cancer cells, as mentioned in a previous mechanistic study. Indeed, the fact that the design of the compounds is based on EGFR inhibition and the observation of such a result has created the need to elucidate the EGFR enzyme mechanics not only in silico but also experimentally.

[0140] Table 3. Mitochondrial membrane polarisation% and depolarisation% results of the compounds that are the subject of the invention

[0141] Mitochondrial membrane polarisation and depolarisation effects of the compounds were determined on A549 cells. Evaluation of EGFR inhibition

[0142] ICso values of the EGFR inhibition test are shown in Table 5. The ICso value of gefitinib used as a positive control was calculated as 4.169±0.156 nM. The most active compounds are Compound 2 (5.298±0.164 nM), Compound 4 (5.46±0.221 nM), Compound 6 (2.670±0.124 nM) and Compound 7 (2.191 ±0.908 nM). These compounds have two common properties. The first is the presence of the quinazolin-4(3 / - / )- on ring. Another property is that compounds other than Compound 4 have aromatic structures with halogen atoms.

[0143] Table 4. EGFR inhibition results of the compounds that are the subject of the invention

[0144] For each compound, the experiment was performed 4 times.

[0145] Interpretation of molecular docking and dynamics simulation studies Docking results were realised across a variety of activity pathways. In all studies, the best molecule - protein complex compatibility (exposure) was taken into account. The MDS studies were carried out based on these complexes obtained.

[0146] Evaluation of docking and dynamics simulation results on the caspase-3 enzyme

[0147] The docking poses are given in Figure 28 and the observed bonds are given in Table 6. In previous studies, amino acids Arg64, Ser120, Hist 21 , Gly122, Gln161 , Cys163, Tyr204, Ser205, Trp206, Arg207, Asn208, Ser209, Ser249 and Phe250 were identified as binding site amino acids. According to the results, it was observed that A / -aminotriazole compounds (Compounds 6, 7 and 8) showed similar types of interactions with amino acids Arg64 (Asn52-Gly66 cycle), Hie121 , Gly122 (B-sheet region: Hie121 - Glu 123), Tyr204, Arg207 (Seri 98-Ser213 loop) and Phe256 (Phe247-Pro263 loop amino acids). Among these interactions, only the interactions with Arg207 were also observed in the A / -(4- methoxyphenyl)triazole derivative Compound 3. The main reason for this is that the docking of the molecule differed from A / -aminotriazole derivatives due to the orientation of the bulky group 4- methoxyphenyl group to the Phe250 amino acid in the enzyme binding site, and Compound 3 lost its interaction with Arg64. On the other hand, while A / -aminotriazole derivatives can make 1 or 2 hydrogen bonds with Arg207, it is observed that Compound 3, in addition to hydrogen bonding, makes both ionic, hydrophobic and aromatic hydrogen bonds with its different parts. Additionally, it has been observed that it forms bonds with amino acids Ser120, Trp206, and Trp214. Compound 7 and Compound 8 made hydrogen bonds with amino acids Glu123 and Ser205. It has been determined that compound 6 specifically interacts with amino acids Gln161 (Leu157-Gln161 of the B-layer region) and Cys163. Since all these interactions are in the enzyme binding region, it is suggested that although the Compound 3 derivative showed a different location, the activation effect resulted similar due to its binding with the same loop regions in the enzyme. Moreover, it is thought that the fact that all four compounds bond with nearby amino acids outside the binding site, especially with various cycle amino acids, stabilises the protein-compound complex and thus provides rigidity to the structure. In conclusion, this in silico study confirmed that all four compounds have robust interactions with the Ser198-Ser213 loop, which has been reported to have a key role in caspase-3 activation. The acetamide structure in the compounds can be defined as a pharmacophore structure because it interacts with the amino acids of this cycle.

[0148] On the other hand, Compound 6 is thought to be more active because, unlike the other 3 derivatives, it forms a salt bridge in addition to the hydrogen bond with Arg64 and forms a hydrogen bond with Gin 161 . In addition, it is suggested that the fact that A / -aminotriazole derivatives have an amine group instead of a bulky phenyl group and thus the molecule can be bent into itself more easily by rotamerising is important in adapting to the gap formed between Arg64 and Arg207 (Figure 28-C). Because the arrangement of the acetamide structure of A / -aminotriazole derivatives easily adapts to the gap between Arg64 and Arg207.

[0149] As a result, the docking study of the compounds is in agreement with the experimental results and the structure-effect relationship on the caspase-3 enzyme has been explained. MDS study was carried out by taking compound 6 motifs and the effects of time and environmental changes (water, various ions, etc.) on the structure-activity relationship and the changes resulting from this effect were examined.

[0150] MDS results are shown in figure 29. Of these, A-C belong to the stability values of the complex and D- F belong to the interactions of the complex.

[0151] The stability of the complex is expressed by having the following properties in the time period examined:

[0152] 1 . Rigid protein structures showing small fluctuations in inertia radius (Rg) values [a-helix regions are shown in light red and B-sheet regions are shown in light blue in the root mean square deviation of atomic position (RMSF) plot],

[0153] 2. The root mean square deviation (RMSD) value for the protein structure being in the range of 1 -3 A and the RMSD value of the ligand not being more than 3 times that of the protein,

[0154] 3. No large fluctuations being in RMSF values in rigid structures.

[0155] These 3 items are the key properties in ensuring stability. Additionally, a situation that increases stability is that the fluctuations in the white areas (loop region) in the RMSF graph are damped. This indicates that the cycle amino acids are also stabilised.

[0156] Accordingly, the RMSD value of the compound 6-caspase-3 complex increased to over 1 A after 0.2 ns, and the highest peak was recorded as 2.64 A at 7.60 ns. Since there are no large fluctuations in RMSF and Rg values, it can be said that the complex remained stable throughout the simulation. Additionally, according to the RMSF plot, the fluctuation sizes of rigid structures were recorded between 0.36-0.93 A (Figure 29-A, B and C).

[0157] When the interaction graphs (Figure 5-D, E and F) are examined, Hydrogen bonds (conventional and water-mediated), hydrophobic interactions (TT-TT stacking and n-cation interaction), and ionic interaction (salt bridge formation) were observed between compound 6 and the caspase-3 enzyme. Conventional hydrogen bonding is established with amino acids Arg64, Gln161 , Cys163, Ser205, Trp206, and Arg207, and water-mediated H-bonding amino acids Thr62, Arg64, Ser120, Hist 21 , Gln161 , Tyr204, Ser205, Trp206, Arg207, Asn208, Ser249, Phe250, Ser251 and Phe256. Hydrophobic interactions were observed between amino acids Met61 , Hist 21 , Tyr204, Trp206 and Phe256 and Compound 6. Finally, the salt bridge was formed only with the amino acid Arg64. Among these, the most striking interactions are with the amino acids Arg64, Cys163, Ser205 and Arg207 due to their continuity. However, according to the order of interaction strengths, H-bond between Arg207 and acetamide oxygen (143%), H-bond between Cys163 and benzimidazole nitrogen (99%), H-bond between Ser2O5 and the hydrogen of N- aminotriazole nitrogen (99%), water-mediated H-bond between Arg64 and acetamide nitrogen (69%), H-bond (63%) between Trp206 and quinazoline nitrogen (N1 ), water-mediated H-bond between Seri 20 and acetamide nitrogen (61 %), water-mediated H-bond between Arg207 and the hydrogen of N- aminotriazole nitrogen (53%), salt bridge between Arg64 and acetamide nitrogen (50%), water -mediated H-bond between acetamide nitrogen (42%), TT-TT stacking between Phe256 and quinazoline ring (42%), TT-TT stacking between His121 and the benzothiazole ring (40%), TT-TT stacking between Tyr204 and the quinazoline ring (36%) and water-mediated H-bond between Arg207 and the triazole nitrogen (N2) (20%) were noted.

[0158] Based on the frequency and bond strength of these interactions, it has been observed that

[0159] • the acetamide residue is an important caspase-3 pharmacophore structure due to its strong interactions with Arg64 and Arg207, especially H-bonding with the 204-209 loop amino acids,

[0160] • combining this pharmacophore structure with a non-bulky triazole and a benzothiazole to increase lipophilicity has a positive effect on the activity through Hist 21 , Gln161 , Cys163, Trp206 and Arg207,

[0161] • and finally, the quinazolin-4(3 / - / )-on ring, due to its exposure to the solvent effect, especially the TT-TT stacking with Phe256, and the benzothiazole ring, due to its continuous H-bond formation with Cys163, have an activity-enhancing effect.

[0162] In the light of this information, one of the structural modifications to be made for caspase-3 activation is changes on the quinazolin-4(3 / - / )-on structure that can interact with the solvent. Here, compounds that will be obtained as a result of acylation at the 6th and 7th positions, as in tyrosine kinase inhibitors (- tinibs), or the addition of polar but non-aromatic structures with straight chains of heteroatoms (such as etheric), suitable as hydrogen bond acceptors, are predicted to have an increasing effect on caspase -3 activation. On the other hand, the A / -aminotriazole structure should be kept constant as an ideal structure. It may be suggested that the changes to be made in the benzothiazole ring should be aimed at improving solubility properties, not for binding to amino acids.

[0163] Table 5. Compound-caspase-3 interaction sequence of the compounds that are the subject of the invention

[0164] Evaluation of docking and dynamics simulation results on the EGFR protein

[0165] The docking poses of the compounds found to be effective at concentrations lower than 10 nM as a result of the experimental activity are shown in Figure 30 and the observed bonds are shown in Table 7.

[0166] According to the literature, amino acids 791 -796, defined as the hinge region connecting the N and C lobes of the receptor, have an important role on the activity. It is observed that clinically used active substances such as gefitinib, which settle in this region, make hydrogen bonds with the hydrogen of the nitrogen in the main chain of Met793, and the number of bonds is usually one. In addition, the hydrophobic side pocket, defined as the ATP binding site, is surrounded by the side chains of amino acids such as Lys745, Leu788 and Thr790, and it has been observed that the hydrophobic parts (such as aniline) of clinically used drugs are placed in this pocket.

[0167] It has been determined that the compounds that are the subject of the invention bind with Lys745, Arg841 and Asp855 in common. Except for compound 4, the compounds were also observed to bind identically to the hinge amino acids Gln791 and Met793. Since the branched structure [A / -(4- methoxyphenyl)] in Compound 4 surrounds the ATP region, the quinazolin-4(3 / - / )-on part could not approach the Met793 amino acid at the right angle, so it made an H-bond only with Cys797, one of the hinge amino acids. In addition, only Compound 2 interacted with Thr854. Finally, among the compounds, only Compound 7 was found to make aromatic H-bonds with amino acid Ser720, which is a member of the phosphate binding (P loop) domain.

[0168] When the poses of the compounds were examined, it was observed that the two most effective compounds (Compound 6 and Compound 7) were in similar positions, and although they showed relative shifts due to the fluorine / chlorine difference, they made similar interactions in both the ATP binding region and the hinge region, and that the chain structures in gefitinib derivatives (such as morpholinopropoxy) are located in a similar way, that is, they extend outside the receptor and become open to interaction with the solvent region.

[0169] As a result, it has been reported that inhibition of the EGFR pathway causes depolarisation of the mitochondrial membrane, which in turn causes activation of caspase-3, especially for non-small cell lung cancer metastasis. In vitro and in silico studies performed for all mechanistic purposes so far are in harmony, and the behaviour of compounds against proteins at the molecular level has been explained with in silico studies. In addition to all these, considering the ICso and apoptosis inductions obtained as a result of MTT, it is suggested that the most potent compound is Compound 6. Therefore, in order to explain the structure-activity relationship, a molecular dynamics simulation was performed using Compound 6 as a model.

[0170] MDS results are shown for compound 8I-EGFR complex in Figure 31 . When the stability indicators (Figure 31 -A, B and C) of the compound 6-EGFR complex are examined, the Rg, RMSD and RMSF values are found to be appropriate. For this reason, it can be said that the complex is stable. Therefore, according to Figure 31 -D, E and F graphs, the most stable interactions of Compound 6 were observed as direct hydrogen bonding with Lys745, Met793, Thr854 and Asp855, as water-mediated hydrogen bond with Lys745 and Thr790, and as n-cation with Arg841 . Although there was a break in the interaction with Lys745 in the 55-60 ns interval, it was observed that more interactions with this amino acid occurred later. Considering the structure-activity relationship obtained from the molecular docking result, it has been observed that the A / -aminotriazole derivatives synthesised in the Compound 6-EGFR complex model are positioned similar to the EGFR inhibitors used in the clinic (such as gefitinib), the stability of the complex with environmental factors is supported and even the interaction strength through water increases. It has also been observed that intramolecular hydrogen bonds occasionally form between the oxygen of quinazolin-4(3 / - / )-on and the hydrogen of the amine group attached to the triazole. Although the frequency of this is low, it can be suggested that it is important in maintaining the relative positions of the two rings relative to the protein.

[0171] It is thought that the hydrogen bond with Lys745, the ATP binding site, has an important role in the activity. Water-mediated H-bond, H-bond and hydrophobic interactions are very important in the bonding relationship. As in the docking study, it became clear that the quinazoline ring and the benzothiazole ring localised well to the hinge region (Gln791 and Met793) and the ATP binding site (Lys745), respectively, and maintained their position over time. In addition, it has been interpreted that the acetamide structure has an important place in its potency due to the bonding of acetamide nitrogen with Asp855 located at the entrance of the ATP binding cleft. It has been observed that the inhibition activity of halogen-containing compounds is higher due to the benzothiazole end being exposed to solvent, maintaining complex stability by interacting with organic (such as phospholipids) and inorganic (such as water, sodium, chlorine, etc. electrolytes) substances in the solvent environment. As in EGFR inhibitors, replacement of the fluorine atom with long-chain polar structures (such as morpholinopropyloxy in gefitinib) can be shown, observationally, among the modifications that may increase the severity of effect.

[0172] Table 6. Compound-EGFR interaction index

[0173] REFERENCES

[0174] [1] Halk Saghgi Genel Mudurlugu. (n.d.). Retrieved December 21 , 2022, from https: / / hsgm.saglik.gov.tr / tr /

[0175] [2] S;, P. H. P. R. A. A. S. (n.d.). Recent updates on third generation EGFR inhibitors and emergence of fourth generation EGFR inhibitors to combat c797s resistance. European journal of medicinal chemistry. Retrieved December 26, 2022, from https: / / pubmed.ncbi.nlm.nih.gov / 28526474 /

[0176] [3] Malleshappa N. Noolvi, Harun M. Patel, Varun Bhardwaj, Ankit Chauhan,

[0177] Synthesis and in vitro antitumor activity of substituted quinazoline and quinoxaline derivatives: Search for anticancer agent,

[0178] European Journal of Medicinal Chemistry, Volume 46, Issue 6, 2011 , Pages 2327-2346,

Claims

CLAIMS1. A quinazolinone derivative compound shown by Formula X with anticancer activity,Formula X wherein R is selected from the formulas below:

2. A compound according to claim 1 having any of the following formulas:• A / -(4-Chlorophenyl)-2-{2-[4-oxoquinazolin-3(4 / 4)-yl]acetyl}hydrazine-1 -carbotioamide (Compound 1 )• A / -(3-Chlorophenyl)-2-{2-[4-oxoquinazolin-3(4 / 4)-yl]acetyl}hydrazine-1 -carbotioamide (Compound 2)• A / -6-Chlorobenzothiazol-2-yl)-2-[(4-(4-methoxyphenyl)-5-{[4-oxoquinazolin-3(4 / 4)- yl]methyl}-4 / 7-1 ,2,4-triazole-3-yl)thio]acetamide (Compound 3)• A / -(Benzothiazol-2-yl)-2-[(4-(4-methoxyphenyl)-5-{[4-oxoquinazolin-3(4 / 4)-yl]methyl}- 4 / 7-1 ,2,4-triazole-3-yl)thio]acetamide (Compound 4)• A / -6-Methylbenzothiazol-2-yl)-2-[(4-(4-methoxyphenyl)-5-{[4-oxoquinazolin-3(4 / 4)- yl]methyl}-4 / 7-1 ,2,4-triazole-3-yl)thio]acetamide (Compound 5)• A / -6-Florobenzothiazol-2-yl)-2-[(4-(4-amino)-5-{[4-oxoquinazolin-3(4 / 4)-yl]methyl}-4 / 7- 1 ,2,4-triazole-3-yl)thio]acetamide (Compound 6)• A / -6-Chlorobenzothiazol-2-yl)-2-[(4-(4-amino)-5-{[4-oxoquinazolin-3(4 / 4)-yl]methyl}-4 / 7- 1 ,2,4-triazole-3-yl)thio]acetamide (Compound 7)• A / -(Benzothiazol-2-yl)-2-[(4-(4-amino)-5-{[4-oxoquinazolin-3(4 / 4)-yl]methyl}-4 / 7-1 ,2,4- triazole-3-yl)thio]acetamide (Compound 8)3. A compound according to claim 1 or 2 denoted by Formula 1 where R=Ri .Formula 14. A compound according to Claim 3, wherein the melting temperature of A / -(4-Chlorophenyl)-2-{2- [4-oxoquinazolin-3(4 / 4)-yl]acetyl}hydrazine-1 -carbotioamide compound (Compound 1 shown in Formula 1 ) is 243-244°C.

5. A compound according to Claim 3, wherein1H-NMR spectrum of the A / -(4-Chlorophenyl)-2-{2- [4-oxoquinazolin-3(4 / 4)-yl]acetyl}hydrazine-1 -carbotioamide compound (Compound 1 shown in Formula 1 ) comprises1H-NMR (300 MHz, DMSO-de): 5 4.79 (s, 2H, N-CH2), 7.43 (d, J= 8.72 Hz, 2H, phenyl Hs.s), 7.55-7.61 (m, 3H, phenyl H2,6 and quinazoline He), 7.73 (d, J= 7.76 Hz, H, quinazoline He), 7.87 (td, Ji=1 .52 Hz, J2=7.65 Hz, H, quinazoline H?), 8.16 (dd, Ji=1 .21 Hz, J2=7.99 HZ, H, quinazoline H5), 8.34 (s, H, quinazoline H2), 9.54 (brs, H, CO-NH-NH-CS-NH), 9.93 (brs, H, CO-NH-NH-CS-NH), 10.60 (brs, H, CS-NH-phenyl) peaks.

6. A compound according to Claim 3, wherein13C-NMR spectrum of the A / -(4-Chlorophenyl)-2-{2- [4-oxoquinazolin-3(4 / - / )-yl]acetyl}hydrazine-1 -carbotioamide compound (Compound 1 shown in Formula 1 ) comprises13C-NMR (75 MHz, DMSO-de): 47.86 (N-CH2), 121 .82, 126.45, 127.30, 127.77, 128.61 , 135.15, 138.41 , 148.49, 148.74, 161 .06, 167.25 (C=O), 181 .02 (C=S) peaks.

7. A compound according to Claim 3, wherein HMRS spectrum of the A / -(4-Chlorophenyl)-2-{2-[4- oxoquinazolin-3(4 / - / )-yl]acetyl}hydrazine-1 -carbotioamide compound (Compound 1 shown in Formula 1 ) comprises 388.0643 peaks for HRMS (-m / z): [M+H]+: C17H14N5O2SCI.

8. A compound according to claims 1 or 2 denoted by Formula 2 where R=R2.Formula 29. A compound according to Claim 2, wherein the melting temperature of A / -(3-Chlorophenyl)-2-{2- [4-oxoquinazolin-3(4 / - / )-yl]acetyl}hydrazine-1 -carbotioamide (Compound 2 shown by Formula 2) is 243-244°C.

10. A compound according to Claim 8, wherein1H-NMR spectrum of the A / -(3-Chlorophenyl)-2-{2- [4-oxoquinazolin-3(4 / - / )-yl]acetyl}hydrazine-1 -carbotioamide (Compound 2 shown by Formula 2) comprises1H-NMR (300 MHz, DMSO-de): 6 4.80 (s, 2H, N-CH2), 7.24 (d, J= 7.31 Hz, H, phenyl H4), 7.40 (t, J=8.03 Hz, H, phenyl H5), 7.56-7.61 (m, 2H, phenyl H6 and quinazoline H6), 7.72- 7.75 (m, 2H, phenyl H2 and quinazoline H8), 7.87 (td, J1 =1 .48 Hz, J2=7.67 Hz, H, quinazoline H7), 8.16 (dd, J1 =1 .16 Hz, J2=7.97 Hz, H, quinazoline H5), 8.36 (s, H, quinazoline H2), 9.54 (brs, H, CO-NH-NH-CS-NH), 10.02 (brs, H, CO-NH-NH-CS-NH), 10.64 (brs, H, CS-NH-phenyl) peaks.

11. A compound according to Claim 8, wherein13C-NMR spectrum of the A / -(3-Chlorophenyl)-2-{2- [4-oxoquinazolin-3(4 / - / )-yl]acetyl}hydrazine-1 -carbotioamide (Compound 2 shown by Formula 2) comprises13C-NMR (75 MHz, DMSO-de): 47.99, 121 .80, 123.79, 124.82, 125.31 , 126.38, 127.79, 130.32, 132.76, 135.18, 140.93 148.51 , 148.70, 161 .13, 167.26, 170.92 (C=O), 180.87 (C=S) peaks.

12. A compound according to Claim 8, wherein HMRS spectrum of the A / -(3-Chlorophenyl)-2-{2-[4- oxoquinazolin-3(4 / - / )-yl]acetyl}hydrazine-1 -carbotioamide (Compound 2 shown by Formula 2) comprises 388.0636 peaks for HRMS (-m / z): [M+H]+: C17H14N5O2SCI.

13. A compound according to claim 1 or 2 denoted by Formula 3 where R= R3.Formula 314. A compound according to Claim 13, wherein the melting temperature of A / -(6- Chlorobenzothiazol-2-yl)-2-[(4-(4-methoxyphenyl)-5-{[4-oxoquinazolin-3(4 / - / )-yl]methyl}-4 / 7-1 ,2,4-triazol-3-yl)thio]acetamide compound (compound 3 shown in Formula 3) is 274-275°C.

15. A compound according to Claim 13, wherein1H-NMR spectrum of the A / -(6-Chlorobenzothiazol- 2-yl)-2-[(4-(4-methoxyphenyl)-5-{[4-oxoquinazolin-3(4 / - / )-yl]methyl}-4 / 7-1 ,2,4-triazol-3- yl)thio]acetamide compound (compound 3 shown in Formula 3) comprises1H-NMR (300 MHz, DMSO-ofe): 5 3.83 (s, 3H, OCH3), 3.95 (s, 2H, S-CH2), 5.16 (s, 2H, N-CH2), 7.1 1 -7.18 (m, 3H, phenyl Hs.s and benzothiazole Hs) 7.34 (d, 4=8.56 Hz, H, benzothiazole H7), 7.48 (d, 4=8.79 Hz, 2H, phenyl H2,e), 7.56 (t, 4=7.55 Hz, H, quinazoline He), 7.67-7.71 (m, 2H, quinazoline He and benzothiazole H4), 7.86 (t, 4=7.91 Hz, H, quinazoline H7), 8.1 1 (d, 4=7.90 Hz, H, quinazoline Hs), 8.36 (s, H, quinazoline H2) peaks.

16. A compound according to Claim 13, wherein13C-NMR spectrum of A / -(6-Chlorobenzothiazol-2- yl)-2-[(4-(4-methoxyphenyl)-5-{[4-oxoquinazolin-3(4 / - / )-yl]methyl}-4 / 7-1 ,2,4-triazol-3- yl)thio]acetamide compound (compound 3 shown in Formula 3) comprises13C-NMR (75 MHz, DMSO-ofe): 40.82 (S-CH2), 41 .12 (N-CH2), 56.04 (OCH3), 1 15.57, 119.83, 120.48, 120.51 , 121 .88, 124.47, 124.74, 125.36, 126.50, 127.71 , 128.95, 135.09, 148.32, 149.89, 151 .62, 153.38, 160.26, 160.67, 169.43, 172.31 (C=O) peaks.

17. A compound according to Claim 13, wherein HMRS spectrum of the A / -(6-Chlorobenzothiazol-2- yl)-2-[(4-(4-methoxyphenyl)-5-{[4-oxoquinazolin-3(4 / - / )-yl]methyl}-4 / 7-1 ,2,4-triazol-3- yl)thio]acetamide compound (compound 3 shown in Formula 3) comprises 590.0824 peaks for HRMS (-m / z): [M+H]+: C27H2oN703S2CI.

18. A compound according to claim 1 or 2 denoted by Formula 4 where R= R4.Formula 419. A compound according to Claim 18, wherein the melting temperature of A / -(Benzothiazol-2-yl)- 2-[(4-(4-methoxyphenyl)-5-{[4-oxoquinazolin-3(4 / - / )-yl]methyl}-4 / 7-1 ,2,4-triazole-3- yl)thio]acetamide compound (Compound 4 shown in Formula 4) is 243-244°C.

20. A compound according to Claim 18, wherein1H-NMR spectrum of the A / -(Benzothiazol-2-yl)-2-[(4-(4-methoxyphenyl)-5-{[4-oxoquinazolin-3(4 / - / )-yl]methyl}-4 / 7-1 ,2,4-triazole- 3- yl)thio]acetamide compound (Compound 4 shown in Formula 4) comprises1H-NMR (300 MHz, DMSO-ofe): 5 3.82 (s, 3H, OCH3), 4.07 (s, 2H, S-CH2), 5.16 (s, 2H, N-CH2), 7.08-7.14 (m, 3H, phenyl H3,s and benzothiazole Hs), 7.26 (td, Ji= 1 .12, J 2= 7.61 Hz, H, benzothiazole H4), 7.48 (d, J= 8.78 Hz, 2H, phenyl H2,e), 7.50-7.58 (m, 2H, quinazoline He and benzothiazole Hs), 7.69-7.76 (m, 2H, quinazoline Hs and benzothiazole H7), 7.85 (td, Ji= 1 .44 Hz, J2= 7.63 Hz, H, quinazoline H7), 8.09 (dd, Ji= 1 .10 Hz, J2= 8.14 Hz, H, quinazoline Hs), 8.36 (s, H, quinazoline H2) peaks.21 . A compound according to Claim 18, wherein13C-NMR spectrum of the A / -(Benzothiazol-2-yl)-2-[(4-(4-methoxyphenyl)-5-{[4-oxoquinazolin-3(4 / - / )-yl]methyl}-4 / 7-1 ,2,4-triazole- 3- yl)thio]acetamide compound (Compound 4 shown in Formula 4) comprises13C-NMR (75 MHz, DMSO-ofe): 40.75 (S-CH2), 41 .13 (N-CH2), 56.04 (O-CH2), 1 15.58, 1 19.74, 121 .49, 121 .86, 122.00, 125.20, 125.37, 126.50, 127.7137, 128.93, 132.79, 135.08, 148.30, 150.19, 151 .90, 152.67, 160.26, 160.72, 164.73, 170.16 (C=O) peaks.

22. A compound according to Claim 18, wherein HMRS spectrum of the A / -(Benzothiazol-2-yl)-2-[(4-(4-methoxyphenyl)-5-{[4-oxoquinazolin-3(4 / - / )-yl]methyl}-4 / 7-1 ,2,4-triazole- 3- yl)thio]acetamide compound (Compound 4 shown in Formula 4) comprises 556.1220 peaks for HRMS spektrumunun, C27H2I N7O3S2.

23. A compound according to claim 1 or 2 denoted by Formula 5 where R= Rs.Formula 524. A compound according to Claim 23, wherein the melting temperature of A / -(6- Methylbenzothiazol-2-yl)-2-[(4-(4-methoxyphenyl)-5-{[4-oxoquinazolin-3(4 / - / )-yl]methyl}-4 / 7-1 .2.4-triazol-3-yl)thio]acetamide compound (Compound 5 shown by Formula 5) is 254-255°C.

25. A compound according to Claim 23, wherein1H-NMR spectrum of the A / -(6-Methylbenzothiazol-2-yl)-2-[(4-(4-methoxyphenyl)-5-{[4-oxoquinazolin-3(4 / - / )-yl]methyl}-4 / 7-1 ,2,4- triazol-3- yl)thio]acetamide compound (Compound 5 shown by Formula 5) comprises1H-NMR (300 MHz, DMSO-ofe): 6 2.35 (s, 3H, CH3), 3.82 (s, 3H, OCH3), 4.05 (s, 2H, S-CH2), 5.16 (s, 2H, N-CH2), 7.07 (dd, Ji=1 .00 Hz, 42=8.29 Hz, benzothiazole H5), 7.12 (d, 4=8.91 Hz, 2H, phenyl H3,5), 7.40 (d, 4=8.15 Hz, H, benzothiazole H7), 7.48 (d, 4=8.88 Hz, 2H, phenyl H2,6), 7.53-7.58 (m, 2H, quinazoline He and benzothiazole H4), 7.70 (d, 4=7.96 Hz, H, quinazoline Hs), 7.85 (td, 4?=1 .36 Hz, 42=7.67 Hz, H, quinazoline H7), 8.10 (dd, 4 / =0.99 Hz, 4 =7.90 Hz, H, quinazoline Hs), 8.36 (s, H, quinazoline H2) peaks.

26. A compound according to Claim 23, wherein13C-NMR spectrum of the A / -(6- Methylbenzothiazol-2-yl)-2-[(4-(4-methoxyphenyl)-5-{[4-oxoquinazolin-3(4 / - / )-yl]methyl}-4 / 7-1 .2.4- triazol-3-yl)thio]acetamide compound (Compound 5 shown by Formula 5) comprises13C- NMR (75 MHz, DMSO-rfe): 21 .44 (CH3), 40.75 (S-CH2), 41 .14 (N-CH2), 56.04 (O-CH3), 1 15.58, 1 19.43, 121 .30, 121 .86, 125.20, 126.49, 126.65, 127.71 , 128.92, 131.14, 132.93, 135.08, 148.07, 148.30, 151 .89, 152.70, 160.26, 160.71 , 163.97, 169.92 (C=O) peaks.

27. A compound according to Claim 23, wherein HRMS spectrum of the A / -(6-Methylbenzothiazol-2- yl)-2-[(4-(4-methoxyphenyl)-5-{[4-oxoquinazolin-3(4 / - / )-yl]methyl}-4 / 7-1 ,2,4- triazol-3- yl)thio]acetamide compound (Compound 5 shown by Formula 5) comprises 570.1368 peaks for HRMS (-m / z): [M+H]+: C28H23N7O3S2.

28. A compound according to claim 1 or 2 denoted by Formula 6 where R= Re.Formula 629. A compound according to Claim 28, wherein the melting temperature of A / -(6- Fluorobenzothiazol-2-yl)-2-[(4-(4-amino)-5-{[4-oxoquinazolin-3(4 / - / )-yl]methyl}-4 / 7-1 ,2,4- triazol- 3-yl)thio]acetamide compound (Compound 6 shown by Formula 6) is 239-240°C.

30. A compound according to Claim 28, wherein1H-NMR spectrum of the A / -(6-Fluorobenzothiazol- 2-yl)-2-[(4-(4-amino)-5-{[4-oxoquinazolin-3(4 / - / )-yl]methyl}-4 / 7-1 ,2,4- triazol-3-yl)thio]acetamide compound (Compound 6 shown by Formula 6) comprises1H-NMR (300 MHz, DMSO-ofe): 4.07 (s, 2H, S-CH2), 5.35 (s, 2H, N-CH2), 6.27 (brs, 2H, N-NH2), 7.14 (td, Ji=2.70 Hz, 42=9.1 1 Hz, H, benzothiazole Hs), 7.53-7.60 (m, 2H, benzothiazole H7 and quinazoline He), 7.66-7.71 (m, 2H, quinazoline He and benzothiazole H4), 7.84 (td, 4?=1 .49 Hz, 4 =7.67 Hz, H, quinazoline H7), 8.14 (dd, 4?=1 .19 Hz, 42=7.95 Hz, H, quinazoline Hs), 8.47 (s, H, quinazoline H2) peaks.31 . A compound according to Claim 28, wherein13C-NMR spectrum of the A / -(6-Fluorobenzothiazol- 2-yl)-2-[(4-(4-amino)-5-{[4-oxoquinazolin-3(4 / - / )-yl]methyl}-4 / 7-1 ,2,4- triazol-3-yl)thio]acetamide compound (Compound 6 shown by Formula 6) comprises13C-NMR (75 MHz, DMSO-ofe): 38.14 (S-CH2), 40.29 (N-CH2), 107.81 ve 108.13, 1 13.29 ve 1 13.61 , 120.77, 120.89, 121 .96, 126.57, 127.70, 133.70, 133.84, 135.05, 146.60, 148.33, 152.53, 153.00, 156.82, 159.97 ve 160.56, 163.83, 170.52 (C=O) peaks.

32. A compound according to Claim 23, wherein HRMS spectrum of the A / -(6-Fluorobenzothiazol-2- yl)-2-[(4-(4-amino)-5-{[4-oxoquinazolin-3(4 / - / )-yl]methyl}-4 / 7-1 ,2,4- triazol-3-yl)thio]acetamide compound (Compound 6 shown by Formula 6) comprises 483.0819 peaks for HRMS (-m / z): [M+H]+: C20H15N8O2S2F.

33. A compound according to claim 1 or 2 denoted by Formula 7 where R= R7.Formula 734. A compound according to Claim 33, wherein the melting temperature of A / -(6- Chlorobenzothiazol-2-yl)-2-[(4-(4-amino)-5-{[4-oxoquinazolin-3(4 / - / )-yl]methyl}-4 / 7-1 ,2,4-triazol- 3-yl)thio]acetamide compound (Compound 7 shown by Formula 7) is 208-209°C.

35. A compound according to Claim 33, wherein1H-NMR spectrum of the A / -(6-Chlorobenzothiazol- 2-yl)-2-[(4-(4-amino)-5-{[4-oxoquinazolin-3(4 / - / )-yl]methyl}-4 / 7-1 ,2,4- triazol-3-yl)thio]acetamide compound (Compound 7 shown by Formula 7) comprises1H-NMR (300 MHz, DMSO-ofe): 6 3.89 (s, 2H, S-CH2), 5.34 (s, 2H, N-CH2), 6.31 (brs, 2H, N-NH2), 7.20 (dd, Ji=1 .95 Hz, 4^8.59 Hz, H, benzothiazole Hs), 7.43 (d, J= 8.53 Hz, H, quinazoline Hs), 7.56 (t, J= 7.57 Hz, H, quinazoline He), 7-70-7.73 (m, 2H, benzothiazole H? and benzothiazole H4), 7.85 (t, 4=7.65 Hz, H, quinazoline H7), 8.15 (d, 4=7.96 Hz, H, quinazoline Hs), 8.47 (s, H, quinazoline H2) peaks.

36. A compound according to Claim 33, wherein13C-NMR spectrum of the N-(6-Chlorobenzothiazol- 2-yl)-2-[(4-(4-amino)-5-{[4-oxoquinazolin-3(4 / - / )-yl]methyl}-4 / 7-1 ,2,4- triazol-3-yl)thio]acetamide compound (Compound 7 shown by Formula 7) comprises13C-NMR (75 MHz, DMSO-ofe): 40.59 (S-CH2), 120.16, 120.63, 121 .97, 124.89, 125.01 , 126.03, 126.58, 127.70, 134.94, 135.07, 148.33, 148.50, 149.61 , 152.30, 153.38, 160.53, 168.83, 172.86 (C=O) peaks.

37. A compound according to Claim 23, wherein HRMS spectrum of the N-(6-Chlorobenzothiazol-2- yl)-2-[(4-(4-amino)-5-{[4-oxoquinazolin-3(4 / - / )-yl]methyl}-4 / 7-1 ,2,4- triazol-3-yl)thio]acetamide compound (Compound 7 shown by Formula 7) comprises 499.0526 peaks for HRMS (-m / z): [M+H]+: C2OHI5N802S2CI.

38. A compound according to claim 1 or 2 denoted by Formula 8 where R= Rs.Formula 839. A compound according to Claim 38, wherein the melting temperature of A / -(Benzothiazol-2-yl)- 2-[(4-(4-amino)-5-{[4-oxoquinazolin-3(4 / - / )-yl]methyl}-4 / 7-1 ,2,4-triazole- 3-yl)thio]acetamide compound (Compound 8 shown by Formula 8) is 221 -222°C.

40. A compound according to Claim 38, wherein1H-NMR spectrum of the A / -(Benzothiazol-2-yl)-2- [(4-(4-amino)-5-{[4-oxoquinazolin-3(4 / - / )-yl]methyl}-4 / 7-1 ,2,4-triazole- 3-yl)thio]acetamide compound (Compound 8 shown by Formula 8) comprises1H-NMR (300 MHz, DMSO-ofe): 6 3.91 (s, 2H, S-CH2), 5.36 (s, 2H, N-CH2), 6.35 (brs, 2H, N-NH2), 7.03 (td, Ji= 0.97 Hz, J2= 7.47 Hz, H, benzothiazole Hs), 7.21 (td, 4;= 1 .16, J2= 7.6 Hz, H, benzothiazole H4), 7.47 (d, 4= 7.97 Hz, H, benzothiazole Hs), 7.56 (td, Ji= 1 .10 Hz, J2= 7.53 Hz, H, quinazoline He), 7.65-7.73 (m, 2H, quinazoline Hs and benzothiazole H7), 7.87 (td, Ji= 1 .55 Hz, J2= 7.99 Hz, H, quinazoline H7), 8.15 (dd, Ji= 1 .26 Hz, J2= 7.96 Hz, H, quinazoline Hs), 8.49 (s, H, quinazoline H2) peaks.

41. A compound according to Claim 38, wherein13C-NMR spectrum of the A / -(Benzothiazol-2-yl)-2- [(4-(4-amino)-5-{[4-oxoquinazolin-3(4 / - / )-yl]methyl}-4 / 7-1 ,2,4-triazole- 3-yl)thio]acetamide compound (Compound 8 shown by Formula 8) comprises13C-NMR (75 MHz, DMSO-ofe): 39.47(S-CH2), 40.64 (N-CH2), 1 19.23, 121.22, 121 .99, 124.89, 126.58, 127.71 , 133.18, 135.06, 148.36, 148.52, 150.69, 152.32, 153.43, 157.44, 160.44, 160.54, 168.05, 172.34 (C=O) peaks.

42. A compound according to Claim 23, wherein HRMS spectrum of the A / -(Benzothiazol-2-yl)-2- [(4-(4-amino)-5-{[4-oxoquinazolin-3(4 / - / )-yl]methyl}-4 / 7-1 ,2,4-triazole- 3-yl)thio]acetamide compound (Compound 8 shown by Formula 8) comprises 465.0910 peaks for HRMS (-m / z): [M+H]+: C20H16N8O2S2.

43. Synthesis method of a compound according to any one of the Claims 3-12, comprising the process steps of: i. mixing anthranilic acid with a mol of formamide equivalent to 1 .2 times the anthranilic acid used in the oil bath, and controlling the reaction in this process by thin layer chromatography (TLC), and then terminating the reaction by pouring the reaction mixture into ice water; afterwards, washing the precipitated part with water, filtering and drying, and crystallising the dried precipitated part from hexane after drying to obtain 4-quinazolinone or by reacting anthranilic acid with a mol of formamide equivalent to 1 .2 times the anthranilic acid used in the microwave and controlling the reaction in this process with TLC, and then terminating the reaction by pouring the reaction mixture into ice water; then, obtaining 4-quinazolinone by washing the precipitated part with water, filtering, drying and crystallizing the dried precipitated part from hexane, ii. dissolving 4-quinazolinone in acetone and adding 1 .5 times the mole of potassium carbonate (K2CO3) to the reaction flask as 4-quinazolinone used; then, adding 1 .1 times mol of 4-quinazolinone and ethyl 2-bromoacetate to the mixture, reacting the mixture with a reversing cooling apparatus and completing the reaction with TLC, and after the end of the reaction, evaporating the acetone from the mixture and washing the precipitated part with water and filtering it to obtain ethyl 2-[4-oxoquinazolin-3(4 / - / )-yl]acetate,Hi. dissolving ethyl 2-[4-oxoquinazolin-3(4 / - / )-yl]acetate in ethanol and adding 1.5 times mol of hydrazine monohydrate / ethanol solution as 2-[4-oxoquinazolin-3(4 / - / )-yl]acetate to the solution portion by portion and keeping the resulting mixture at room temperature overnight, then, completing the reaction with TLC and separating the precipitated part by filtration and drying, then, crystallising the dried precipitated part with ethanol and obtaining 2-[4- oxoquinazolin-3(4 / - / )-yl]acetohydrazide, iv. adding 4-chlorophenylisothiocyanate or 3-chlorophenylisothiocyanate, one of the alkyl / aryl isothiocyanate derivatives dissolved in alcohol, in equal moles to the 2-[4-oxoquinazolin- 3(4 / - / )-yl]acetohydrazide compound dissolved in ethanol in an ice bath and controlling the reaction with TLC; then, washing the precipitated part with alcohol, filtering and drying, and after recrystallising the dried precipitate from alcohol, obtaining A / -(4-Chlorophenyl)-2-{2-[4- oxoquinazolin-3(4 / - / )-yl]acetyl}hydrazine-1 -carbotioamide compound (Compound 1 ) or the A / -(3-Chlorophenyl)-2-{2-[4-oxoquinazolin-3(4 / - / )-yl]acetyl}hydrazine-1 -carbotioamide compound (Compound 2).

44. A synthesis method according to claim 43, comprising the steps of:i. mixing 27.428 g, 0.2 mol anthranilic acid with a mol of formamide equivalent to 1 .2 times the anthranilic acid used in the oil bath for 4-8 hours, and controlling the reaction in this process by thin layer chromatography (TLC), and then terminating the reaction by pouring the reaction mixture into ice water; afterwards, washing the precipitated part with water, filtering and drying, and crystallising the dried precipitated part from hexane after drying to obtain 4-quinazolinone or by reacting 27.428 g, 0.2 mol anthranilic acid with a mol of formamide equivalent to 1 .2 times the anthranilic acid used in the microwave at 500 W for 10-20 minutes and controlling the reaction in this process with TLC, and then terminating the reaction by pouring the reaction mixture into ice water; then, obtaining 4-quinazolinone by washing the precipitated part with water, filtering, drying and crystallizing the dried precipitated part from hexane, ii. dissolving 40 g, 274 mmol 4-quinazolinone in acetone and adding 1.5 times the mole of potassium carbonate (K2CO3) to the reaction flask as 4-quinazolinone used; then, adding 1 .1 times mol of 4-quinazolinone and ethyl 2-bromoacetate to the mixture, reacting the mixture with a reversing cooling apparatus and completing the reaction with TLC, and after the end of the reaction, evaporating the acetone from the mixture and washing the precipitated part with water and filtering it to obtain ethyl 2-[4-oxoquinazolin-3(4 / - / )- yl]acetate,Hi. dissolving 46 g, 198 mmol ethyl 2-[4-oxoquinazolin-3(4 / - / )-yl]acetate in ethanol and adding 1 .5 times mol of hydrazine monohydrate / ethanol solution as 2-[4-oxoquinazolin-3(4 / - / )- yl]acetate to the solution portion by portion and keeping the resulting mixture at room temperature overnight, then, completing the reaction with TLC and separating the precipitated part by filtration and drying, then, crystallising the dried precipitated part with ethanol and obtaining 2-[4-oxoquinazolin-3(4 / - / )-yl]acetohydrazide, iv. adding 4-chlorophenylisothiocyanate or 3-chlorophenylisothiocyanate, one of the alkyl / aryl isothiocyanate derivatives dissolved in alcohol, in equal moles to the 20 g, 92 mmol 2-[4- oxoquinazolin-3(4 / - / )-yl]acetohydrazide compound dissolved in ethanol in an ice bath and controlling the reaction with TLC; then, washing the precipitated part with alcohol, filtering and drying, and after recrystallising the dried precipitate from alcohol, obtaining A / -(4- Chlorophenyl)-2-{2-[4-oxoquinazolin-3(4 / - / )-yl]acetyl}hydrazine-1 -carbotioamide compound (Compound 1 ) or the A / -(3-Chlorophenyl)-2-{2-[4-oxoquinazolin-3(4 / - / )-yl]acetyl}hydrazine- 1 -carbotioamide compound (Compound 2).

45. A synthesis method according to claim 44, comprising the steps of: i. mixing 27.428 g, 0.2 mol anthranilic acid with a mol of formamide equivalent to 1 .2 times the anthranilic acid used in the oil bath for 6 hours, and controlling the reaction in this process by thin layer chromatography (TLC), and then terminating the reaction by pouring the reaction mixture into ice water; afterwards, washing the precipitated part with water, filtering and drying, and crystallising the dried precipitated part from hexane after d rying to obtain 4-quinazolinone or by reacting 27.428 g, 0.2 mol anthranilic acid with a mol of formamide equivalent to 1 .2 timesthe anthranilic acid used in the microwave at 500 W for 15 minutes and controlling the reaction in this process with TLC, and then terminating the reaction by pouring the reaction mixture into ice water; then, obtaining 4-quinazolinone by washing the precipitated part with water, filtering, drying and crystallizing the dried precipitated part from hexane, ii. dissolving 40 g, 274 mmol 4-quinazolinone in acetone and adding 1 .5 times the mole of potassium carbonate (K2CO3) to the reaction flask as 4-quinazolinone used; then, adding 1 .1 times mol of 4-quinazolinone and ethyl 2-bromoacetate to the mixture, reacting the mixture with a reversing cooling apparatus and completing the reaction with TLC, and after the end of the reaction, evaporating the acetone from the mixture and washing the precipitated part with water and filtering it to obtain ethyl 2-[4-oxoquinazolin-3(4 / - / )-yl]acetate,Hi. dissolving 46 g, 198 mmol ethyl 2-[4-oxoquinazolin-3(4 / - / )-yl]acetate in ethanol and adding 1 .5 times mol of hydrazine monohydrate / ethanol solution as ethyl 2-[4-oxoquinazolin-3(4 / - / )- yl]acetate to the solution portion by portion and keeping the resulting mixture at room temperature overnight, then, completing the reaction with TLC and separating the precipitated part by filtration and drying, then, crystallising the dried precipitated part with ethanol and obtaining 2-[4-oxoquinazolin-3(4 / - / )-yl]acetohydrazide, iv. adding 4-chlorophenylisothiocyanate or 3-chlorophenylisothiocyanate, one of the alkyl / aryl isothiocyanate derivatives dissolved in alcohol, in equal moles to the 20 g, 92 mmol 2-[4- oxoquinazolin-3(4 / - / )-yl]acetohydrazide compound dissolved in ethanol in an ice bath and controlling the reaction with TLC; then, washing the precipitated part with alcohol, filtering and drying, and after recrystallising the dried precipitate from alcohol, obtaining A / -(4-Chlorophenyl)- 2-{2-[4-oxoquinazolin-3(4 / - / )-yl]acetyl}hydrazine-1 -carbotioamide compound (Compound 1 ) or the A / -(3-Chlorophenyl)-2-{2-[4-oxoquinazolin-3(4 / - / )-yl]acetyl}hydrazine-1 -carbotioamide compound (Compound 2).

46. A method according to any one of the Claims 43-45, wherein, in case 4- chlorophenylisothiocyanate is used as alkyl / aryl isothiocyanate derivative in process step (iv), N- (4-Chlorophenyl)-2-{2-[4-oxoquinazolin-3(4 / - / )-yl]acetyl}hydrazine-1 -carbotioamide compound (Compound 1 ) is synthesised.

47. A method according to Claim 43 or 44, wherein, in case 3-chlorophenylisothiocyanate is used as alkyl / aryl isothiocyanate derivative in process step (iv), N-(3-Chlorophenyl)-2-{2-[4- oxoquinazolin-3(4 / - / )-yl]acetyl}hydrazine-1 -carbotioamide compound (Compound 2) is synthesised.

48. Synthesis method of a compound according to any one of the Claims 13-42, comprising the process steps of: i. mixing anthranilic acid with a mol of formamide equivalent to 1 .2 times the anthranilic acid used in the oil bath, and controlling the reaction in this process by thin layer chromatography (TLC), and then terminating the reaction by pouring the reaction mixture into ice water; afterwards, washing the precipitated part with water, filtering and drying, and crystallising the dried precipitated part from hexane after drying to obtain 4-quinazolinone or by reacting anthranilic acid with a mol of formamide equivalent to 1 .2 times the anthranilic acid used inthe microwave and controlling the reaction in this process with TLC, and then terminating the reaction by pouring the reaction mixture into ice water; then, obtaining 4-quinazolinone by washing the precipitated part with water, filtering, drying and crystallizing the dried precipitated part from hexane, ii. dissolving 4-quinazolinone in acetone and adding 1 .5 times the mole of potassium carbonate (K2CO3) to the reaction flask as 4-quinazolinone used; then, adding 1 .1 times mol of 4-quinazolinone and ethyl 2-bromoacetate to the mixture, reacting the mixture with a reversing cooling apparatus and completing the reaction with TLC, and after the end of the reaction, evaporating the acetone from the mixture and washing the precipitated part with water and filtering it to obtain ethyl 2-[4-oxoquinazolin-3(4 / - / )-yl]acetate,Hi. dissolving ethyl 2-[4-oxoquinazolin-3(4 / - / )-yl]acetate in ethanol and adding 1.5 times mol of hydrazine monohydrate / ethanol solution as 2-[4-oxoquinazolin-3(4 / - / )-yl]acetate to the solution portion by portion and keeping the resulting mixture at room temperature overnight, then, completing the reaction with TLC and separating the precipitated part by filtration and drying, then, crystallising the dried precipitated part with ethanol and obtaining 2-[4- oxoquinazolin-3(4 / - / )-yl]acetohydrazide, iv. adding equal moles of 4-methoxyphenylisothiocyanate dissolved in alcohol onto the 2-[4- oxoquinazolin-3(4 / - / )-yl]acetohydrazide compound dissolved in ethanol in an ice bath and controlling the reaction with TLC; then, washing the precipitated part with alcohol, filtering and drying. and obtaining A / -(4-Methoxyphenyl)-2-{2-[4-oxoquinazolin-3(4 / - / )- yl]acetyl}hydrazine-1 -carbotioamide after recrystallising the dried precipitate from alcohol, v. boiling the A / -(4-Methoxyphenyl)-2-{2-[4-oxoquinazolin-3(4 / - / )-yl]acetyl}hydrazine-1 - carbotioamide and sodium hydroxide (NaOH) in ethanol solution with reflux apparatus and finishing the reaction with TLC; after the end of the reaction, pouring the mixture into ice water and adjusting the pH of the mixture to 7 with dilute hydrochloric acid (HCI) solution, then, filtering the precipitated part and washing with water, then crystallising the precipitated part from ethanol to obtain compound 3-{[4-(4-Methoxyphenyl)-5-thioxo-4,5-dihydro-1 H-1 .2.4-triazol-3-yl]methyl}quinazolin-4(3 / 7)-on, vi. dissolving 2-[4-Oxoquinazolin-3(4 / - / )-yl]acetohydrazide and sodium hydroxide (NaOH) in ethanol solution and adding 1 .2 times the amount of carbon disulphide (CS2) to the resulting mixture in an ice bath and keeping the resulting mixture in an ice bath and then at room temperature and boiling the mixture under reflux after precipitations are observed in the mixture; then, the completing reaction with TLC, after the reaction is completed, pouring the mixture into ice water and adjusting the pH of the mixture to 7 with dilute hydrochloric acid (HCI) solution; then, filtering the precipitated part and washing with water, and then crystallising the precipitated part is from ethanol and obtaining the 3-[(5-Thioxo-4,5-dihydro-1 .3.4-oxadiazol-2-yl)methyl]quinazolin-4(3 / - / )-on compound,vii. dissolving the 3-[(5-Thioxo-4,5-dihydro-1 ,3,4-oxadiazol-2-yl)methyl]quinazolin-4(3 / 7)-on compound in ethanol and adding 2 times the mol of 3-[(5-Thioxo-4,5-dihydro-1 ,3,4- oxadiazol-2-yl)methyl]quinazolin-4(3 / 7)-one to hydrazine monohydrate and boiling the resulting mixture; then completing the reaction with TLC, and after the reaction is completed, washing the precipitated part with ethanol and filtering and crystallizing the precipitated part from alcohol to obtain the 3-[(4-Amino-5-thioxo-4,5-dihydro-7 / 7-1 ,2,4- triazol-3-yl)methyl)quinazolin-4(3 / 7)-on compound, viii. mixing the obtained 3-{[4-(4-Methoxyphenyl)-5-thioxo-4,5-dihydro- 7 / 7-1 ,2,4-triazol-3- yl]methyl}quinazolin-4(3 / 7)-on and 3-[(4-Amino-5-thioxo-4,5-dihydro- 7 / 7-1 ,2,4-triazol-3- yl)methyl)quinazolin-4(3 / 7)-on compounds with 3-{[4-(4-Methoxyphenyl)-5-thioxo-4,5- dihydro- 7 / 7-1 ,2,4-triazol-3-yl]methyl}quinazolin-4(3 / 7)-on and 1 times mole of A / -(6- chlorobenzothiazol-2-yl)-2-chloroacetamide, A / -(benzothiazol-2-yl)-2-chloroacetamide or N- (6-methylbenzothiazol-2-yl)-2-chloroacetamide derivatives among the 2-chloro-A / -aryl acetamide derivatives of 3-{[4-(4-Methoxyphenyl)-5-thioxo-4,5-dihydro- 7 / 7-1 ,2,4-triazol-3- yl]methyl}quinazolin-4(3 / 7)-on substance and with 3-[(4-Amino-5-thioxo-4,5-dihydro- 7 / 7-1 .2.4-triazol-3-yl)methyl)quinazolin-4(3H)-on and 1 times mole of A / -(6-fluorobenzothiazol- 2-yl)-2-chloroacetamide, A / -(6-chlorobenzothiazol-2-yl)-2-chloroacetamide or N- (benzothiazol-2-yl)-2-chloroacetamide derivatives among 2-chloro-A / -aryl acetamide derivatives of 3-[(4-Amino-5-thioxo-4,5-dihydro- 7 / 7-1 ,2,4-triazol-3-yl)methyl)quinazolin- 4(3 / 7)-on substance in acetone at room temperature under the catalyst of potassium carbonate (K2CO3) 1 .5 times the molar amount of mercapto derivative; after the end of the reaction, evaporating the solvent in the mixture and washing the solid part is with water and filtering, and then crystallizing the dried solid part from ethanol and synthesising A / -(4- Chlorophenyl)-2-{2-[4-oxoquinazolin-3(4 / 7)-yl]acetyl}hydrazine-1 -carbotioamide (Compound 1 ), A / -(3-Chlorophenyl)-2-{2-[4-oxoquinazolin-3(4 / 7)-yl]acetyl}hydrazine-1 - carbotioamide (Compound 2), A / -6-Chlorobenzothiazol-2-yl)-2-[(4-(4-methoxyphenyl)-5-{[4- oxoquinazolin-3(4 / 7)-yl]methyl}-4 / 7-1 ,2,4-triazole-3-yl)thio]acetamide (Compound 3), N- (Benzothiazol-2-yl)-2-[(4-(4-methoxyphenyl)-5-{[4-oxoquinazolin-3(4 / 7)-yl]methyl}-4 / 7-1 .2.4-triazole-3-yl)thio]acetamide (Compound 4), A / -6-Methylbenzothiazol-2-yl)-2-[(4-(4- methoxyphenyl)-5-{[4-oxoquinazolin-3(4 / 7)-yl]methyl}-4 / 7-1 ,2,4-triazole-3-yl)thio]acetamide (Compound 5), A / -6-Florobenzothiazol-2-yl)-2-[(4-(4-amino)-5-{[4-oxoquinazolin-3(4 / 7)- yl]methyl}-4 / 7-1 ,2,4-triazole-3-yl)thio]acetamide (Compound 6), A / -6-Chlorobenzothiazol-2- yl)-2-[(4-(4-amino)-5-{[4-oxoquinazolin-3(4 / 7)-yl]methyl}-4 / 7-1 ,2,4-triazole-3- yl)thio]acetamide (Compound 7) or A / -(Benzothiazol-2-yl)-2-[(4-(4-amino)-5-{[4- oxoquinazolin-3(4 / 7)-yl]methyl}-4 / 7-1 ,2,4-triazole-3-yl)thio]acetamide (Compound 8).

49. A synthesis method according to claim 48, comprising the steps of: i. mixing 27.428 g, 0.2 mol anthranilic acid with a mol of formamide equivalent to 1 .2 times the anthranilic acid used in the oil bath for 4-8 hours, and controlling the reaction in this process by thin layer chromatography (TLC), and then terminating the reaction by pouringthe reaction mixture into ice water; afterwards, washing the precipitated part with water, filtering and drying, and crystallising the dried precipitated part from hexane after drying to obtain 4-quinazolinone or by reacting 27.428 g, 0.2 mol anthranilic acid with a mol of formamide equivalent to 1 .2 times the anthranilic acid used in the microwave at 500 W for 10-20 minutes and controlling the reaction in this process with TLC, and then terminating the reaction by pouring the reaction mixture into ice water; then, obtaining 4-quinazolinone by washing the precipitated part with water, filtering, drying and crystallizing the dried precipitated part from hexane, ii. dissolving 40 g, 274 mmol 4-quinazolinone in acetone and adding 1.5 times the mole of potassium carbonate (K2CO3) to the reaction flask as 4-quinazolinone used; then, adding 1 .1 times mol of 4-quinazolinone and ethyl 2-bromoacetate to the mixture, reacting the mixture with a reversing cooling apparatus and completing the reaction with TLC, and after the end of the reaction, evaporating the acetone from the mixture and washing the precipitated part with water and filtering it to obtain ethyl 2-[4-oxoquinazolin-3(4 / - / )- yl]acetate,Hi. dissolving 46 g, 198 mmol ethyl 2-[4-oxoquinazolin-3(4 / - / )-yl]acetate in ethanol and adding 1 .5 times mol of hydrazine monohydrate / ethanol solution as 2-[4-oxoquinazolin-3(4 / - / )- yl]acetate to the solution portion by portion and keeping the resulting mixture at room temperature overnight, then, completing the reaction with TLC and separating the precipitated part by filtration and drying, then, crystallising the dried precipitated part with ethanol and obtaining 2-[4-oxoquinazolin-3(4 / - / )-yl]acetohydrazide, iv. adding equal moles of 4-methoxyphenylisothiocyanate dissolved in alcohol onto the 20 g, 92 mmol 2-[4-oxoquinazolin-3(4 / - / )-yl]acetohydrazide compound dissolved in ethanol in an ice bath and controlling the reaction with TLC; then, washing the precipitated part with alcohol, filtering and drying, and obtaining A / -(4-Methoxyphenyl)-2-{2-[4-oxoquinazolin- 3(4 / - / )-yl]acetyl}hydrazine-1 -carbotioamide after recrystallising the dried precipitate from alcohol, v. boiling the 30g, 78 mmol A / -(4-Methoxyphenyl)-2-{2-[4-oxoquinazolin-3(4 / - / )- yl]acetyl}hydrazine-1 -carbotioamide and 2M sodium hydroxide (NaOH) in ethanol solution with reflux apparatus for 1 -6 hours and finishing the reaction with TLC; after the end of the reaction, pouring the mixture into ice water and adjusting the pH of the mixture to 7 with dilute hydrochloric acid (HCI) solution, then, filtering the precipitated part and washing with water, then crystallising the precipitated part from ethanol to obtain compound 3-{[4-(4- Methoxyphenyl)-5-thioxo-4,5-dihydro-1 H-1 ,2,4-triazol-3-yl]methyl}quinazolin-4(3 / )-on, vi. dissolving 20 g, 92 mmol 2-[4-Oxoquinazolin-3(4 / - / )-yl]acetohydrazide and sodium hydroxide (NaOH) in ethanol solution and adding 1 .2 times the amount of carbon disulphide (CS2) to the resulting mixture in an ice bath and keeping the resulting mixture in an ice bath for 30 minutes and then at room temperature for 10-60 minutes and boiling the mixture under reflux for 2 hours after precipitations are observed in the mixture; then , the completing reaction with TLC, after the reaction is completed, pouring the mixture into ice water andadjusting the pH of the mixture to 7 with dilute hydrochloric acid (HCI) solution; then, filtering the precipitated part and washing with water, and then crystallising the precipitated part is from ethanol and obtaining the 3-[(5-Thioxo-4,5-dihydro-1 ,3,4-oxadiazol-2- yl)methyl]quinazolin-4(3 / 7)-on compound, vii. dissolving the 17 g, 65 mmol 3-[(5-Thioxo-4,5-dihydro-1 ,3,4-oxadiazol-2- yl)methyl]quinazolin-4(3 / 7)-on compound in ethanol and adding 2 times the mol of 3-[(5- Thioxo-4,5-dihydro-1 ,3,4-oxadiazol-2-yl)methyl]quinazolin-4(3 / 7)-one to hydrazine monohydrate and boiling the resulting mixture; then completing the reaction with TLC, and after the reaction is completed, washing the precipitated part with ethanol and filtering and crystallizing the precipitated part from alcohol to obtain the 3-[(4-Amino-5-thioxo-4,5- dihydro- 7 / 7-1 ,2,4-triazol-3-yl)methyl)quinazolin-4(3 / 7)-on compound, viii. mixing the obtained 3-{[4-(4-Methoxyphenyl)-5-thioxo-4,5-dihydro- 7 / 7-1 ,2,4-triazol-3- yl]methyl}quinazolin-4(3 / 7)-on and 3-[(4-Amino-5-thioxo-4,5-dihydro- 7 / 7-1 ,2,4-triazol-3- yl)methyl)quinazolin-4(3 / 7)-on compounds with 0.3 g, 0.82 mmol 3-{[4-(4-Methoxyphenyl)- 5-thioxo-4,5-dihydro- 7 / 7-1 ,2,4-triazol-3-yl]methyl}quinazolin-4(3H)-on and 1 times mole of A / -(6-chlorobenzothiazol-2-yl)-2 -chloroacetamide, A / -(benzothiazol-2-yl)-2 -chloroacetamide or A / -(6-methylbenzothiazol-2-yl)-2-chloroacetamide derivatives among the 2-chloro-A / -aryl acetamide derivatives of 3-{[4-(4-Methoxyphenyl)-5-thioxo-4,5-dihydro- 7 / 7-1 ,2,4-triazol-3- yl]methyl}quinazolin-4(3 / 7)-on substance and with 0.3 g, 1 mmol 3-[(4-Amino-5-thioxo-4,5- dihydro-1 H-1 ,2,4-triazol-3-yl)methyl)quinazolin-4(3 / 7)-on and 1 times mole of A / -(6- fluorobenzothiazol-2-yl)-2 -chloroacetamide, A / -(6-chlorobenzothiazol-2-yl)-2- chloroacetamide or A / -(benzothiazol-2-yl)-2-chloroacetamide derivatives among 2-chloro-N- aryl acetamide derivatives of 3-[(4-Amino-5-thioxo-4,5-dihydro- 7 / 7-1 ,2,4-triazol-3- yl)methyl)quinazolin-4(3 / 7)-on substance in acetone at room temperature for 2-6 hours under the catalyst of potassium carbonate (K2CO3) 1 .5 times the molar amount of mercapto derivative; after the end of the reaction, evaporating the solvent in the mixture and washing the solid part is with water and filtering, and then crystallizing the dried solid part from ethanol and synthesising A / -(4-Chlorophenyl)-2-{2-[4-oxoquinazolin-3(4 / 7)- yl]acetyl}hydrazine-1 -carbotioamide (Compound 1 ), A / -(3-Chlorophenyl)-2-{2-[4- oxoquinazolin-3(4 / 7)-yl]acetyl}hydrazine-1 -carbotioamide (Compound 2), A / -6-Chlorobenzothiazol-2-yl)-2-[(4-(4-methoxyphenyl)-5-{[4-oxoquinazolin-3(4 / 7)-yl]methyl}- 4 / 7-1 ,2,4-triazole-3-yl)thio]acetamide (Compound 3), A / -(Benzothiazol-2-yl)-2-[(4-(4- methoxyphenyl)-5-{[4-oxoquinazolin-3(4 / 7)-yl]methyl}-4 / 7-1 ,2,4-triazole-3-yl)thio]acetamide (Compound 4), A / -6-Methylbenzothiazol-2-yl)-2-[(4-(4-methoxyphenyl)-5-{[4-oxoquinazolin- 3(4 / 7)-yl]methyl}-4 / 7-1 ,2,4-triazole-3-yl)thio]acetamide (Compound 5), A / -6-Florobenzothiazol-2-yl)-2-[(4-(4-amino)-5-{[4-oxoquinazolin-3(4 / 7)-yl]methyl}-4 / 7-1 ,2,4- triazole-3-yl)thio]acetamide (Compound 6), A / -6-Chlorobenzothiazol-2-yl)-2-[(4-(4-amino)- 5-{[4-oxoquinazolin-3(4 / 7)-yl]methyl}-4 / 7-1 ,2,4-triazole-3-yl)thio]acetamide (Compound 7) or A / -(Benzothiazol-2-yl)-2-[(4-(4-amino)-5-{[4-oxoquinazolin-3(4 / 7)-yl]methyl}-4 / 7-1 ,2,4- triazole-3-yl)thio]acetamide (Compound 8).

50. A synthesis method according to claim 49, comprising the steps of: i. mixing 27.428 g, 0.2 mol anthranilic acid with a mol of formamide equivalent to 1 .2 times the anthranilic acid used in the oil bath for 6 hours, and controlling the reaction in this process by thin layer chromatography (TLC), and then terminating the reaction by pouring the reaction mixture into ice water; afterwards, washing the precipitated part with water, filtering and drying, and crystallising the dried precipitated part from hexane after drying to obtain 4-quinazolinone or by reacting 27.428 g, 0.2 mol anthranilic acid with a mol of formamide equivalent to 1 .2 times the anthranilic acid used in the microwave at 500 W for 15 minutes and controlling the reaction in this process with TLC, and then terminating the reaction by pouring the reaction mixture into ice water; then, obtaining 4-quinazolinone by washing the precipitated part with water, filtering, drying and crystallizing the dried precipitated part from hexane, ii. dissolving 40 g, 274 mmol 4-quinazolinone in acetone and adding 1.5 times the mole of potassium carbonate (K2CO3) to the reaction flask as 4-quinazolinone used; then, adding 1 .1 times mol of 4-quinazolinone and ethyl 2-bromoacetate to the mixture, reacting the mixture with a reversing cooling apparatus and completing the reaction with TLC, and after the end of the reaction, evaporating the acetone from the mixture and washing the precipitated part with water and filtering it to obtain ethyl 2-[4-oxoquinazolin-3(4 / - / )- yl]acetate,Hi. dissolving 46 g, 198 mmol ethyl 2-[4-oxoquinazolin-3(4 / - / )-yl]acetate in ethanol and adding 1 .5 times mol of hydrazine monohydrate / ethanol solution as 2-[4-oxoquinazolin-3(4 / - / )- yl]acetate to the solution portion by portion and keeping the resulting mixture at room temperature overnight, then, completing the reaction with TLC and separating the precipitated part by filtration and drying, then, crystallising the dried precipitated part with ethanol and obtaining 2-[4-oxoquinazolin-3(4 / - / )-yl]acetohydrazide, iv. adding equal moles of 4-methoxyphenylisothiocyanate dissolved in alcohol onto the 20 g, 92 mmol 2-[4-oxoquinazolin-3(4 / - / )-yl]acetohydrazide compound dissolved in ethanol in an ice bath and controlling the reaction with TLC; then, washing the precipitated part with alcohol, filtering and drying, and obtaining A / -(4-Methoxyphenyl)-2-{2-[4-oxoquinazolin- 3(4 / - / )-yl]acetyl}hydrazine-1 -carbotioamide after recrystallising the dried precipitate from alcohol, v. boiling the 30g, 78 mmol A / -(4-Methoxyphenyl)-2-{2-[4-oxoquinazolin-3(4 / - / )- yl]acetyl}hydrazine-1 -carbotioamide and 2M sodium hydroxide (NaOH) in ethanol solution with reflux apparatus for 2 hours and finishing the reaction with TLC; after the end of the reaction, pouring the mixture into ice water and adjusting the pH of the mixture to 7 with dilute hydrochloric acid (HCI) solution, then, filtering the precipitated part and washing with water, then crystallising the precipitated part from ethanol to obtain compound 3-{[4-(4- Methoxyphenyl)-5-thioxo-4,5-dihydro-1 H-1 ,2,4-triazol-3-yl]methyl}quinazolin-4(3 / 7)-on, vi. dissolving 20 g, 92 mmol 2-[4-Oxoquinazolin-3(4 / - / )-yl]acetohydrazide and sodium hydroxide (NaOH) in ethanol solution and adding 1 .2 times the amount of carbon disulphide(CS2) to the resulting mixture in an ice bath and keeping the resulting mixture in an ice bath for 30 minutes and then at room temperature for 30 minutes and boiling the mixture under reflux for 2 hours after precipitations are observed in the mixture; then, the completing reaction with TLC, after the reaction is completed, pouring the mixture into ice water and adjusting the pH of the mixture to 7 with dilute hydrochloric acid (HCI) solution; then, filtering the precipitated part and washing with water, and then crystallising the precipitated part is from ethanol and obtaining the 3-[(5-Thioxo-4,5-dihydro-1 ,3,4-oxadiazol-2- yl)methyl]quinazolin-4(3 / 4)-on compound, vii. dissolving the 17 g, 65 mmol 3-[(5-Thioxo-4,5-dihydro-1 ,3,4-oxadiazol-2- yl)methyl]quinazolin-4(3 / 4)-on compound in ethanol and adding 2 times the mol of 3-[(5- Thioxo-4,5-dihydro-1 ,3,4-oxadiazol-2-yl)methyl]quinazolin-4(3 / 4)-one to hydrazine monohydrate and boiling the resulting mixture; then completing the reaction with TLC, and after the reaction is completed, washing the precipitated part with ethanol and filtering and crystallizing the precipitated part from alcohol to obtain the 3-[(4-Amino-5-thioxo-4,5- dihydro-1 H-1 ,2,4-triazol-3-yl)methyl)quinazolin-4(3 / 4)-on compound, viii. mixing the obtained 3-{[4-(4-Methoxyphenyl)-5-thioxo-4,5-dihydro-1 H-1 ,2,4-triazol-3- yl]methyl}quinazolin-4(3 / 4)-on and 3-[(4-Amino-5-thioxo-4,5-dihydro-1 H-1 ,2,4-triazol-3- yl)methyl)quinazolin-4(3 / - / )-on compounds with 0.3 g, 0.82 mmol 3-{[4-(4-Methoxyphenyl)- 5-thioxo-4,5-dihydro-1 H-1 ,2,4-triazol-3-yl]methyl}quinazolin-4(3 / 4)-on and 1 times mole of N-(6-chlorobenzothiazol-2-yl)-2 -chloroacetamide, N-(benzothiazol-2-yl)-2 -chloroacetamide or A / -(6-methylbenzothiazol-2-yl)-2-chloroacetamide derivatives among the 2-chloro-N-aryl acetamide derivatives of 3-{[4-(4-Methoxyphenyl)-5-thioxo-4,5-dihydro-1 H-1 ,2,4-triazol-3- yl]methyl}quinazolin-4(3 / 4)-on substance and with 0.3 g, 1 mmol 3-[(4-Amino-5-thioxo-4,5- dihydro-1 H-1 ,2,4-triazol-3-yl)methyl)quinazolin-4(3 / 4)-on and 1 times mole of A / -(6- fluorobenzothiazol-2-yl)-2 -chloroacetamide, A / -(6-chlorobenzothiazol-2-yl)-2- chloroacetamide or A / -(benzothiazol-2-yl)-2-chloroacetamide derivatives among 2-chloro-A / - aryl acetamide derivatives of 3-[(4-Amino-5-thioxo-4,5-dihydro- / / 7-1 ,2,4-triazol-3- yl)methyl)quinazolin-4(3 / - / )-on substance in acetone at room temperature for 2 hours under the catalyst of potassium carbonate (K2CO3) 1 .5 times the molar amount of mercapto derivative; after the end of the reaction, evaporating the solvent in the mixture and washing the solid part is with water and filtering, and then crystallizing the dried solid part from ethanol and synthesising A / -(4-Chlorophenyl)-2-{2-[4-oxoquinazolin-3(4 / 4)- yl]acetyl}hydrazine-1 -carbotioamide (Compound 1 ), A / -(3-Chlorophenyl)-2-{2-[4- oxoquinazolin-3(4 / 4)-yl]acetyl}hydrazine-1 -carbotioamide (Compound 2), A / -6-Chlorobenzothiazol-2-yl)-2-[(4-(4-methoxyphenyl)-5-{[4-oxoquinazolin-3(4 / 4)-yl]methyl}- 4 / 7-1 ,2,4-triazole-3-yl)thio]acetamide (Compound 3), A / -(Benzothiazol-2-yl)-2-[(4-(4- methoxyphenyl)-5-{[4-oxoquinazolin-3(4 / 4)-yl]methyl}-4 / 7-1 ,2,4-triazole-3-yl)thio]acetamide (Compound 4), A / -6-Methylbenzothiazol-2-yl)-2-[(4-(4-methoxyphenyl)-5-{[4-oxoquinazolin- 3(4 / 4)-yl]methyl}-4 / 7-1 ,2,4-triazole-3-yl)thio]acetamide (Compound 5), A / -6-Florobenzothiazol-2-yl)-2-[(4-(4-amino)-5-{[4-oxoquinazolin-3(4 / 4)-yl]methyl}-4 / 7-1 ,2,4-triazole-3-yl)thio]acetamide (Compound 6), A / -6-Chlorobenzothiazol-2-yl)-2-[(4-(4-amino)- 5-{[4-oxoquinazolin-3(4 / 7)-yl]methyl}-4 / 7-1 ,2,4-triazole-3-yl)thio]acetamide (Compound 7) or A / -(Benzothiazol-2-yl)-2-[(4-(4-amino)-5-{[4-oxoquinazolin-3(4 / 7)-yl]methyl}-4 / 7-1 ,2,4- triazole-3-yl)thio]acetamide (Compound 8).

51. A method according to any of the Claims 48-50, wherein, in case 2-chloro-N-(6- chlorobenzothiazol-2-yl)acetamide is used as 2-chloro-N-aryl acetamide derivative in process step (viii), A / -(6-Chlorobenzothiazol-2-yl)-2-[(4-(4-methoxyphenyl)-5-{[4-oxoquinazolin-3(4 / 7)- yl]methyl}-4 / 7-1 ,2,4- triazol-3-yl)thio]acetamide compound (Compound 3) is synthesised.

52. A method according to any of the Claims 48-50, wherein, in case 2-chloro-N-(benzothiazol-2- yl)acetamide is used as 2-chloro-N-aryl acetamide derivative in process step (viii), N- (Benzothiazol-2-yl)-2-[(4-(4-methoxyphenyl)-5-{[4-oxoquinazolin-3(4 / 7)-yl]methyl}-4 / 7-1 ,2,4- triazole- 3-yl)thio]acetamide compound (Compound 4) is synthesised.

53. A method according to any fo the Claims 48-50, wherein, in case 2-chloro-N-(6- methylbenzothiazol-2-yl)acetamide is used as 2-chloro-N-aryl acetamide derivative in process step (viii), A / -(6-Methylbenzothiazol-2-yl)-2-[(4-(4-methoxyphenyl)-5-{[4-oxoquinazolin-3(4 / 7)- yl]methyl}-4 / 7-1 ,2,4- triazol-3-yl)thio]acetamide compound (Compound 5) is synthesised.

54. A method according to any fo the Claims 48-50, wherein, in case 2-chloro-N-(6- fluorobenzothiazol-2-yl)acetamide is used as 2-chloro-N-aryl acetamide derivative in process step (viii), A / -(6-Fluorobenzothiazol-2-yl)-2-[(4-(4-amino)-5-{[4-oxoquinazolin-3(4 / 7)-yl]methyl}- 4 / 7-1 ,2,4- triazol-3-yl)thio]acetamide compound (Compound 6) is synthesised.

55. A method according to any of the Claims 48-50, wherein, in case 2-chloro-N-(6- chlorobenzothiazol-2-yl)acetamide is used as 2-chloro-N-aryl acetamide derivative in process step (viii), A / -(6-Chlorobenzothiazol-2-yl)-2-[(4-(4-amino)-5-{[4-oxoquinazolin-3(4 / 7)-yl]methyl}- 4 / 7-1 ,2,4- triazol-3-yl)thio]acetamide compound (Compound 7) is synthesised.

56. A method according to any of the Claims 48-50, wherein, in case 2-chloro-N-(benzothiazol-2- yl)acetamide is used as 2-chloro-N-aryl acetamide derivative in process step (viii), N- (Benzothiazol-2-yl)-2-[(4-(4-amino)-5-{[4-oxoquinazolin-3(4 / 7)-yl]methyl}-4 / 7-1 ,2,4-triazole- 3- yl)thio]acetamide compound (Compound 8) is synthesised.

57. A compound according to any one of claims 1 -42 for use in the treatment of cancer.

58. A compound according to any one of claims 1 -42 for use in the treatment of lung cancer.

59. A pharmaceutical composition comprising a compound according to any one of claims 1 -42.

60. A pharmaceutical composition according to claim 59 for use in the treatment of cancer.

61. A pharmaceutical composition according to claim 59 for use in the treatment of lung cancer.

62. An anti-cancer medicament comprising a pharmaceutical composition according to any one of claims 59-61 .

63. A medicament comprising a compound according to any one of claims 1 -42 as active ingredient.

64. A compound obtained by a synthesis method according to any one of claims 43-45.

65. A compound obtained by a synthesis method according to any one of claims 48-50.