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Pyrimidine-type antitumor compound, preparation method and application thereof

A compound and anti-tumor technology, applied in the field of medicine, can solve problems such as reducing bioavailability

Inactive Publication Date: 2019-05-03
中国医科大学
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, in addition to pyrimidine nucleosides, TP can also induce phosphorylation of several nucleoside analogs, reducing their bioavailability

Method used

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  • Pyrimidine-type antitumor compound, preparation method and application thereof
  • Pyrimidine-type antitumor compound, preparation method and application thereof
  • Pyrimidine-type antitumor compound, preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0089] Preparation of N'-phenyl-3-(uracil-5-sulfonamido)benzohydrazide (A1).

[0090] a. Preparation of uracil-5-sulfonyl chloride: Add uracil (6g, 53.55mmoL) and thionyl chloride (10mL, 89.22mmoL) into a 100mL reaction flask at 25°C, react at room temperature for 1.5h, add Chlorosulfonic acid (16g, 133.82mmoL) was reacted at 60°C for 4h, and continued to react at 75°C for 7h; the reaction solution was added to ice water, and a precipitate was precipitated, filtered with suction, washed with water several times, and dried at 50°C to obtain 4.50g of a white solid, yield : 70%.

[0091] b. Preparation of N'-(3-formic acid phenyl)uracil-5-sulfonamide: Add uracil-5-sulfonyl chloride (4g, 19.05mmol) in 20ml reaction bottle at 25°C In DMF, react with m-aminobenzoic acid (3.0 g, 22.86 mmol) in pyridine (0.6 g, 28.57 mmol) at room temperature for 5 h to obtain 5.00 g of the target product with a yield of 79.96%.

[0092] c. Preparation of N'-phenyl-3-(uracil-5-carboxamido)benzohydra...

Embodiment 2

[0095] Preparation of N'-(2-methylphenyl)-3-(uracil-5-sulfonamido)benzohydrazide (A2).

[0096] Using o-methylphenylhydrazine hydrochloride as raw material, synthesize uracil-5-sulfonyl chloride according to the steps of Example 1a, and prepare N'-(2-methylphenyl)-3-(urine Pyrimidine-5-sulfonamido)benzohydrazide, light yellow solid 2.08g, yield: 62.34%.

[0097] 1 H NMR (600MHz, DMSO-d 6)δ11.84(s.,1H),11.59(s.,1H),10.36(d,J=2.8Hz,2H),8.10(s,1H),7.62(d,J=2.1Hz,2H), 7.40(t, J=8.1Hz, 1H), 7.30(dd, J=1.1, 8.1Hz, 1H), 7.26(d, J=2.6Hz, 1H), 7.09-6.98(m, 2H), 6.72-6.62 (m,2H),2.20(s,3H); MS(ESI,m / z):414.08[M-H] - .

Embodiment 3

[0099] Preparation of N'-(3-methylphenyl)-3-(uracil-5-sulfonamido)benzohydrazide (A3).

[0100] Using m-methylphenylhydrazine as a raw material, synthesize uracil-5-sulfonyl chloride according to the step 1a of Example 1a, and prepare N'-(3-methylphenyl)-2-(uracil -5-sulfonamido)benzohydrazide (A3) off-white solid 2.58g, yield: 77.33%.

[0101] 1 H NMR (600MHz, DMSO-d 6 )δ10.47(s,1H),10.41(s,1H),8.11(s,1H),7.74(s,1H),7.71(d,J=5.8Hz,1H),7.64(s,1H), 7.59(d, J=7.7Hz, 1H), 7.41-7.40(m, 2H), 7.39(s, 1H), 7.32(d, J=7.3Hz, 1H), 2.38(s, 3H); MS(ESI ,m / z):414.10[M-H] - .

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PUM

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Abstract

The invention belongs to the field of medicines and particularly relates to a pyrimidine-type antitumor compound, a preparation method and an application thereof. In the invention, the medicinal effect characters of a pyrimidine analogue and a TP inhibitor are analyzed; the invention is to design a series of novel compounds, having the bio-effects of both compounds, through a splicing principle. Pharmacological research proves that the compounds have certain inhibition activity on human lung cancer A549 cells, human ovarian cancer OVCAR-3 cells and human gastric cancer SGC-7901 cells.

Description

technical field [0001] The invention belongs to the field of medicine, and specifically relates to a pyrimidine antitumor compound and a preparation method and application thereof. Background technique [0002] Cancer is a malignant tumor originating from epithelial tissue. It is a disease characterized by rapid cell proliferation and metastasis. The death rate ranks first among all diseases. According to the latest global cancer data released by the International Agency for Research on Cancer, there were 14.1 million new cancer patients in the world in 2012, and the annual growth rate will increase by 11%. Therefore, the treatment of cancer has been paid close attention to all over the world. [0003] At present, there are four main ways to treat cancer in the adjacent bed: surgery, radiation therapy, chemotherapy, and immunotherapy. Compared with the other three methods, chemical drug treatment is generally painless, and its lethality to cancer cells is difficult to achi...

Claims

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Application Information

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IPC IPC(8): C07D239/60A61P35/00
Inventor 孟繁浩李馨阳梁经纬何鑫曹崇李帅
Owner 中国医科大学