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A class of quinazoline compounds and their application as immunosuppressants

A kind of quinazoline, immunosuppressive technology, applied in the field of medicine

Active Publication Date: 2016-10-05
CHONGQING UNIV OF TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

JAK3 inhibitors currently on the market or in clinical research all have a series of side effects due to simultaneous inhibition of other JAK subtype kinases

Method used

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  • A class of quinazoline compounds and their application as immunosuppressants
  • A class of quinazoline compounds and their application as immunosuppressants
  • A class of quinazoline compounds and their application as immunosuppressants

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0030] Example 1: Preparation of 4-{N-butyl-N-[(1H-tetrazol-5-yl]biphenyl)methyl]amine}-6-methoxyquinazoline:

[0031] In the first step, add 1.00g of compound 1-trityl-4'-bromomethyl-[1,1]-biphenyl-2-tetrazole and 10mL of tetrahydrofuran into a 25mL double-necked round bottom flask, and stir until The solid was completely dissolved, and 0.72 mL of butylamine was added to react at room temperature for 3 hours, monitored by TLC. After the reaction was completed, the solvent was removed from the obtained solution by rotary evaporation, and the obtained product was dissolved in 25 mL of chloroform. Wash the organic phase (20mL×3) with dilute NaOH solution, anhydrous Na 2 SO 4 Dry and remove solvent in vacuo. Silica gel column chromatography (petroleum ether: ethyl acetate: triethylamine = 2:1:0.01 and ethyl acetate: methanol = 10:1 gradient elution) gave 0.87 g of a colorless viscous solid (88%), It is the product of the first step.

[0032] In the second step, 753 mg (1.37 ...

Embodiment 2

[0034] Example 2: Preparation of 4-{N-butyl-N-[(1H-tetrazol-5-yl]biphenyl)methyl]amine}-6,-hydroxyquinazoline:

[0035] The final product (247mg, 0.53mmol) prepared in Example 1 was added into 1.5mL trimethylsilicon iodide solution, heated to reflux and stirred at room temperature for about 24h. Add excess MeOH solution to the mixture, stir at room temperature for about 12h, after the reaction is complete, spin off the solvent, extract with 30mL of chloroform, take the organic phase with a saturated aqueous solution of sodium bisulfite, pass it through a silica gel column (ethyl acetate:methanol=8:1 ), spin-dried to obtain the target product (147mg, 62%).

Embodiment 3

[0036] Example 3: Preparation of 4-{N-butyl-N-[(1H-tetrazol-5-yl]biphenyl)methyl]amine}-6,7-dimethoxyquinazoline:

[0037]In the second step (the first step is the same as in Example 1 and will not be repeated), take 1.098g (2.0mmol) of the compound 1-trityl-4'-butylaminomethyl-[1,1]-biphenyl- Dissolve 2-tetrazole in 13mL N,N-dimethylformamide, add 0.5mL triethylamine, add 344mg (1.54mmol) 6,7-dimethoxy-4-chloroquinazoline to the mixture, 50°C Under reaction for 96 hours, TLC monitoring, the resulting mixture was added 130mL ethyl acetate, the resulting organic phase was washed with saturated sodium chloride (30ml × 2), anhydrous sodium sulfate, potassium bicarbonate dried, concentrated, passed through a silica gel column (petroleum ether: ethyl acetate = 1:1), rotary evaporation, and drying to obtain 847 mg of white solid, which is the product of the second step, with a yield of 55%.

[0038] In the third step, 2.5 ml of 10% HCl solution was added to the tetrahydrofuran solu...

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Abstract

The invention relates to a quinazoline compound. The structure of the compound is represented by a general formula shown in the specification. In the general formula, R is one of hydrogen, alkyl groups, alkenyl groups, alkynyl groups, aralkyl groups, formyl groups, halogens, nitro groups, amino groups, amido groups, acylamino groups, sulfonamide groups, hydroxy groups and alkoxy groups. The compound is a 4-{N-butyl-N-[(2'-1H-tetratriazol-5-yl)biphenyl)methyl]amine}quinazoline compound, and belongs to the field of medical immunology. The invention also relates to an application of the compound in the preparation of drugs for inhibiting Jurkat cell proliferation. The compound can well inhibit the Jurkat cell proliferation, and the drugs for inhibiting Jurkat cell proliferation prepared by using the compound can be used for autoimmune diseases and transplant rejection.

Description

technical field [0001] The invention relates to quinazoline compounds, a preparation method of the compounds, and their activity in inhibiting JAK3 tyrosine protein kinase, and are used for treating various diseases related to immunity and autoimmunity, and belong to the technical field of medicine. Background technique [0002] Immunity refers to the physiological protective function of the body's physiological defense, self-stabilization and immune surveillance. It is mainly reflected in the body's identification and killing of foreign bacteria, viruses, or tumors and damaged cells produced by the body, so as to ensure the normal operation of the body. When the immune system has an abnormal attack on itself (such as rheumatoid arthritis, systemic lupus erythematosus, autoimmune hemolytic anemia, etc.), or when it is necessary to reduce foreign rejection (such as organ transplantation), immunosuppressant (immunosuppressant) is needed To inhibit cellular and humoral immune ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D403/12A61K31/517A61P37/06A61P19/02A61P29/00A61P17/00A61P1/04A61P1/16A61P7/06A61P3/10
CPCC07D403/12
Inventor 林治华安春红王锐常志超姚爽舒茂王远强胡勇
Owner CHONGQING UNIV OF TECH
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