CN109364081B - Application of pyrimidine derivative in preparation of medicine for treating thyroid cancer - Google Patents

Application of pyrimidine derivative in preparation of medicine for treating thyroid cancer Download PDF

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CN109364081B
CN109364081B CN201811605984.0A CN201811605984A CN109364081B CN 109364081 B CN109364081 B CN 109364081B CN 201811605984 A CN201811605984 A CN 201811605984A CN 109364081 B CN109364081 B CN 109364081B
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thyroid cancer
phenyl
pyrimidine derivative
cancer
medicine
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CN109364081A (en
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刘华平
李月群
金荣
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Shanghai Luotuo Biotechnology Co ltd
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/14—Drugs for disorders of the endocrine system of the thyroid hormones, e.g. T3, T4
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04—Ortho-condensed systems

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Abstract

The invention discloses an application of a pyrimidine derivative in treating thyroid cancer. Thyroid cancer is a high-incidence endocrine malignant tumor, and the incidence rate and mortality data of cancer issued by the cancer prevention and control center of China in 2018 show that about 17 ten thousand cases of thyroid cancer are newly issued in China in 2014, and about 0.8 ten thousand cases of thyroid cancer death are discovered. At present, fewer drugs for effectively treating thyroid cancer are available, and the clinical requirements cannot be met. The invention discovers that the partial pyrimidine derivatives have obvious inhibition effect on human thyroid cancer B-CPAP cells, and can be used for preparing the medicine for treating thyroid cancer; the mother nucleus and the substituent of the pyrimidine derivative both significantly influence the drug effect on thyroid cancer.

Description

Application of pyrimidine derivative in preparation of medicine for treating thyroid cancer
Technical Field
The invention belongs to the field of medicines, and particularly relates to a biological medicine application of a pyrimidine derivative in treatment of thyroid cancer.
Background
Thyroid cancer is a high-incidence endocrine malignancy, and incidence rate and mortality data of cancer issued by the cancer prevention and control center of China in 2018 show that about 17 ten thousand cases of thyroid cancer (about 12.7 ten thousand cases of women and about 4.3 ten thousand cases of men) are newly issued in 2014, and about 0.8 ten thousand cases of thyroid cancer deaths (about 0.5 ten thousand cases of women and about 0.3 ten thousand cases of men) are discovered in 2014.
At present, fewer drugs for effectively treating thyroid cancer are available, and the clinical requirements cannot be met.
Disclosure of Invention
The invention aims to provide a biological medical application of a pyrimidine derivative in treating thyroid cancer.
The technical scheme for realizing the aim of the invention is as follows:
the medical use of a pyrimidine derivative of the chemical structure;
Figure BDA0001922543550000011
wherein, the substituent R is Phenyl, 4-Cl-Phenyl and 2-NO2Phenyl or
Figure BDA0001922543550000012
The medical application of the pyrimidine derivative with the following chemical structure in preparing the medicine for treating thyroid cancer;
Figure BDA0001922543550000013
wherein, the substituent R is Phenyl, 4-Cl-Phenyl and 2-NO2Phenyl or
Figure BDA0001922543550000014
A pharmaceutical preparation for treating thyroid cancer comprises pyrimidine derivatives with the following chemical structure as active ingredients;
Figure BDA0001922543550000015
wherein, the substituent R is Phenyl, 4-Cl-Phenyl and 2-NO2Phenyl or
Figure BDA0001922543550000016
Further, the composition also contains pharmaceutically acceptable auxiliary materials.
The medical use of a pyrimidine derivative of the chemical structure;
Figure BDA0001922543550000021
wherein, the substituent R is Phenyl, 4-Cl-Phenyl and 2-NO2Phenyl or
Figure BDA0001922543550000022
The medical application of the pyrimidine derivative with the following chemical structure in preparing the medicine for treating thyroid cancer;
Figure BDA0001922543550000023
wherein, the substituent R is Phenyl, 4-Cl-Phenyl and 2-NO2Phenyl or
Figure BDA0001922543550000024
A pharmaceutical preparation for treating thyroid cancer comprises pyrimidine derivatives with the following chemical structure as active ingredients;
Figure BDA0001922543550000025
wherein, the substituent R is Phenyl, 4-Cl-Phenyl and 2-NO2Phenyl or
Figure BDA0001922543550000026
Further, the composition also contains pharmaceutically acceptable auxiliary materials.
The medical use of a pyrimidine derivative of the chemical structure;
Figure BDA0001922543550000027
wherein, the substituent R is Phenyl or 4-Cl-Phenyl.
The medical application of the pyrimidine derivative with the following chemical structure in preparing the medicine for treating thyroid cancer;
Figure BDA0001922543550000028
wherein, the substituent R is Phenyl or 4-Cl-Phenyl.
A pharmaceutical preparation for treating thyroid cancer comprises pyrimidine derivatives with the following chemical structure as active ingredients;
Figure BDA0001922543550000029
wherein, the substituent R is Phenyl or 4-Cl-Phenyl.
Further, the composition also contains pharmaceutically acceptable auxiliary materials.
The medical use of a pyrimidine derivative of the chemical structure;
Figure BDA0001922543550000031
wherein, the substituent R is Phenyl, 4-Cl-Phenyl or 4-CH3-Phenyl。
The medical application of the pyrimidine derivative with the following chemical structure in preparing the medicine for treating thyroid cancer;
Figure BDA0001922543550000032
wherein, the substituent R is Phenyl, 4-Cl-Phenyl or 4-CH3-Phenyl。
A pharmaceutical preparation for treating thyroid cancer comprises pyrimidine derivatives with the following chemical structure as active ingredients;
Figure BDA0001922543550000033
wherein, the substituent R is Phenyl, 4-Cl-Phenyl or 4-CH3-Phenyl。
Further, the composition also contains pharmaceutically acceptable auxiliary materials.
The invention has the outstanding advantages that:
the invention discovers that the partial pyrimidine derivatives have obvious inhibition effect on human thyroid cancer B-CPAP cells, and can be used for preparing the medicine for treating thyroid cancer; the mother nucleus and the substituent of the pyrimidine derivative both significantly influence the drug effect on thyroid cancer.
Drawings
FIG. 1 shows the IC50 values for inhibition of human thyroid cancer B-CPAP cell proliferation by pyrimidine derivatives.
Detailed Description
The following detailed description of the present invention is provided in connection with the examples, and for reasons of brevity, the description of the experimental procedures is not intended to be exhaustive, and all parts not specifically described in the experiments are routine procedures well known to those skilled in the art.
First, experimental material
Human thyroid cancer B-CPAP cells cultured in RPMI-1640 containing 10% fetal bovine serum at 37 ℃ in 5% CO2And (4) performing conventional culture in a cell culture box, and selecting cells in a logarithmic growth phase in an experiment.
The pyrimidine derivatives to be tested have the chemical structures shown in the following table, either made by house or purchased, and have a purity of not less than 95%.
Figure BDA0001922543550000041
RPMI-1640 medium, fetal bovine serum was purchased from Gibco.
Second, Experimental methods
MTT method is adopted to test the proliferation inhibition effect of each pyrimidine derivative on human thyroid cancer B-CPAP cells, and the antithyroid effect of each pyrimidine derivative is evaluated according to the IC50 value of the proliferation inhibition activity of each pyrimidine derivative on the B-CPAP cells, and the method specifically comprises the following steps: inoculating human thyroid cancer B-CPAP cells into 96-well plate containing RPMI-1640+ 10% fetal bovine serum culture medium, and culturing at 37 deg.C with 5% CO2Culturing for 24h under the condition, adding the derivative to be tested with the gradient concentration diluted by the culture medium and a blank control into a culture plate, treating for 72h, adding 20 mu L of MTT reagent with the concentration of 5mg/mL into each well, continuing culturing for 4h, removing the supernatant, adding 150 mu L DMSO into each well, shaking for dissolving, measuring the absorbance value (OD570) at the wavelength of 570nm by using a microplate reader, calculating the inhibition rate of each pyrimidine derivative on the thyroid cancer B-CPAP cells according to the following formula, and obtaining the IC50 value by Graphpad fitting.
The inhibition rate (%) was (blank OD 570-experiment OD 570)/blank OD 570X 100%
Third, experimental results
The IC50 values for inhibition of human thyroid cancer B-CPAP cell proliferation for each pyrimidine derivative are shown in table 1 and fig. 1.
TABLE 1 IC50 values for inhibition of human thyroid cancer B-CPAP cell proliferation by pyrimidine derivatives
Figure BDA0001922543550000051
The experimental results show that the pyrimidine derivatives except the pyrimidine derivatives 3, 8 and 13 have obvious inhibition effect on human thyroid cancer B-CPAP cells, and can be used for preparing the medicines for treating thyroid cancer; the mother nucleus and the substituent of the pyrimidine derivative both significantly influence the treatment effect on thyroid cancer.
The foregoing embodiments are provided to illustrate the present invention more fully, but those skilled in the art will appreciate that the scope of the present invention should not be limited to the specific embodiments described above.

Claims (1)

1. The medical application of the pyrimidine derivative with the following chemical structure in preparing the medicine for treating thyroid cancer;
Figure FDA0002576164920000011
wherein, the substituent R is Phenyl, 4-Cl-Phenyl and 2-NO2Phenyl or
Figure FDA0002576164920000012
CN201811605984.0A 2018-12-26 2018-12-26 Application of pyrimidine derivative in preparation of medicine for treating thyroid cancer Active CN109364081B (en)

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