CN-119569738-B - Quinazoline small molecular compound and preparation method and application thereof

Abstract

The invention belongs to the technical field of medicines, and particularly relates to a quinazoline small molecule compound as well as a preparation method and application thereof. The molecular formula of the quinazoline small molecule compound is C 25 H 19 N 3 O, and the structural formula is as follows: The preparation method is characterized in that 6-methoxy-2-naphthaldehyde and 2- (2-aminophenyl-) -1H-benzimidazole react under the heating condition to obtain the product. The quinazoline small molecule compound shows better selective inhibition on PTP1B, has stronger inhibition on HepG2 liver cancer cells at the cell level, and can be applied to preparing medicaments for tumors.

Inventors

• LI XINHUA
• WU LINZHI
• YAN JUANZHI

Assignees

• 太原学院

Dates

Publication Date

20260508

Application Date

20241209

Claims (8)

1. 1. A quinazoline small molecule compound is characterized by having a molecular formula of C 25 H 19 N 3 O and a structural formula of: 。
2. 2. The quinazoline small molecule compound according to claim 1, wherein the quinazoline small molecule compound belongs to a monoclinic system, the space group is P2 1 /n, the unit cell parameters are a= 10.6210 (10) a, b= 10.2037 (8) a, c= 17.5041 (14) a, α=90°, β= 94.986 (5), and γ=90°.
3. 3. The preparation method of the quinazoline small molecule compound according to claim 1 or 2 is characterized by comprising the following steps of dissolving 6-methoxy-2-naphthaldehyde and 2- (2-aminophenyl-) -1H-benzimidazole in methanol, and obtaining the quinazoline small molecule compound through heating reflux.
4. 4. The method for producing a quinazoline small molecule compound according to claim 3, wherein the molar ratio of 6-methoxy-2-naphthaldehyde to 2- (2-aminophenyl) -1H-benzimidazole is 1:1.
5. 5. The method for producing a quinazoline small molecule compound according to claim 3, wherein the temperature of the heat reflux is 60 ℃ for 3 h.
6. 6. Use of a quinazoline small molecule compound according to claim 1 or 2 in the preparation of a PTP1B inhibitor.
7. 7. A PTP1B inhibitor comprising the quinazoline small molecule compound of claim 1 or 2.
8. 8. The use of a quinazoline small molecule compound as claimed in claim 1 or 2 or a PTP1B inhibitor as claimed in claim 7 in the manufacture of a medicament for liver cancer.

Description

Quinazoline small molecular compound and preparation method and application thereof Technical Field The invention belongs to the technical field of medicines, and particularly relates to a quinazoline small molecule compound as well as a preparation method and application thereof. Background Protein Tyrosine Phosphatases (PTPs) are nonmetallic enzymes widely existing in cells, regulate the phosphorylation level of intracellular tyrosine together with protein tyrosine kinase, are expressed in various tissues of a human body, and play an important role in various physiological processes. Once the PTPs are expressed in a disorder, excessive or insufficient tyrosine dephosphorylation may be caused, resulting in the occurrence of many diseases associated with signal transduction disorders including cancer, diabetes, obesity, immune disorders, etc. At present, a great deal of genetics and pharmacology research shows that various PTPs are closely related to human diseases, and some PTPs are hopeful to become therapeutic targets of human diseases. Among the vast family of PTPs, the study and use of PTP1B is most attractive. PTP1B was isolated from human placental tissue in 1988 and was the first successfully isolated PTP, and its crystal structure was first confirmed in 1994, and PTP1B contained 435 amino acid residues, of which 30-278 amino acids constitute the catalytic domain of the enzyme, and was located on the cytoplasmic network via the C-terminal end of 35 proline residues. The main structural features of PTP1B are three highly conserved loop structures, namely the Cys215 containing catalytically active region, the WPD loop and the second binding site. Recent literature reports that PTP1B is over-expressed in breast cancer and liver cancer tissues, and inhibitors of PTP1B may become potential therapeutic drugs. At present, although various small molecule inhibitors of PTP1B have been reported, because the PTPs family has higher homology, especially TCPTP has 74% homology with PTP1B in sequence, inhibitors with high activity and high selectivity are still lacking, so the development of inhibitors with high specificity still has practical significance for treating PTP1B related diseases. Disclosure of Invention In view of the above, the invention aims to overcome the defects in the prior art and provide a quinazoline small molecule compound, and a preparation method and application thereof. In order to achieve the above purpose, the technical scheme of the invention is as follows: A quinazoline small molecule compound has a molecular formula of C 25H19N3 O and a structural formula of: The quinazoline small molecule compound belongs to a monoclinic system, the space group is P2 1/n, and the unit cell parameters are as follows: α=90°,β=94.986(5),γ=90°。 the preparation method of the quinazoline small molecular compound comprises the following steps of dissolving 6-methoxy-2-naphthaldehyde and 2- (2-aminophenyl) -1H-benzimidazole in methanol, and carrying out heating reflux to obtain the quinazoline small molecular compound. Further, the molar ratio of the 6-methoxy-2-naphthaldehyde to the 2- (2-aminophenyl) -1H-benzimidazole is 1:1. Further, the temperature of the heating reflux is 60 ℃ and the time is 3h. The asymmetric unit of the quinazoline small molecule compound comprises a molecule, 6-methoxy-2-naphthaldehyde and 2- (2-aminophenyl-) -1H-benzimidazole are cyclized under the action of heating in the preparation process, a ligand is converted into a 6- (6-methoxy naphthalene-2-yl) -12,12 a-dihydrobenzo [4,5] imidazo [1,2-C ] quinazoline small molecule compound from a Schiff base compound, and simultaneously C-H.cndot.N in one molecule and C-H.cndot.N in the other molecule form a weak interaction molecule to form a one-dimensional chain structure. The application of the quinazoline small molecule compound as a PTP1B inhibitor. A PTP1B inhibitor comprising a quinazoline small molecule compound as described above. The application of the quinazoline small molecule compound or the PTP1B inhibitor in preparing tumor medicaments. Further, the tumor includes liver cancer. Compared with the prior art, the invention has the following beneficial effects: The quinazoline small molecular compound is obtained by reacting 6-methoxy-2-naphthaldehyde with 2- (2-aminophenyl-) -1H-benzimidazole under the heating condition, and has the advantages of simple preparation method, high product purity, crystal structure and high yield which can reach 70 percent. The quinazoline small molecule compound provided by the invention can effectively inhibit PTP1B, has about 5 times of selectivity compared with TCPTP of homology, and has a strong inhibition effect on HepG2 human liver cancer cells. The quinazoline small molecule compounds of the present invention will also be useful as potential candidates for the treatment of PTP 1B-related diseases. Drawings FIG. 1A synthetic route pattern of quinazoline small molecule compounds of the pre