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Preparation method of triazole derivatives and application of triazole derivatives as drugs

A triazole, pharmaceutical technology, applied in the field of drug synthesis, can solve the problem of invalidity of patients

Inactive Publication Date: 2016-05-04
CHINA PHARM UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

There is currently no effective drug treatment for such patients, and traditional chemotherapy and radiotherapy are almost ineffective for patients

Method used

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  • Preparation method of triazole derivatives and application of triazole derivatives as drugs
  • Preparation method of triazole derivatives and application of triazole derivatives as drugs
  • Preparation method of triazole derivatives and application of triazole derivatives as drugs

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0066]

[0067] The synthetic route is:

[0068]

[0069] Reagents and conditions: a) N-bromosuccinimide, dichloromethane, -10°C; b) tert-butylsulfinamide, tetraethyl titanate, tetrahydrofuran acetonitrile, 70°C; c) sodium borohydride , tetrahydrofuran, water, room temperature; d) 3-bromopropyne, sodium hydride, N,N-dimethylformamide, 0 ℃; e) triphosgene, tetrahydrofuran, room temperature; f) phenyl azide, sulfuric acid pentahydrate Copper, sodium ascorbate, dichloromethane, methanol, water, room temperature; g) 3,5-dimethylisoxazole-4-boronic acid pinacol ester, [1,1′-bis(diphenylphosphine) di Ferrocene] palladium dichloride dichloromethane complex, potassium carbonate, toluene, methanol, N,N-dimethylformamide, nitrogen, 80°C.

[0070] a) Dissolve 2-aminobenzophenone (5g, 25.35mmol) in 60ml of dichloromethane, stir in a cold trap at -10°C for 10min, and add N-bromosuccinimide (4.74g, 26.62mmol), continued to react in the cold trap for 2 hours, added 30ml of water, ext...

Embodiment 13

[0081]

[0082] The synthetic route is:

[0083]

[0084] Reagents and conditions: a) Iodomethane, sodium hydride, N,N-dimethylformamide, 0°C.

[0085] a) 6-(3,5-dimethylisoxazole)-4-phenyl-3-((1-phenyl-1H-1,2,3-triazole)methyl)-3, 4-Dihydroquinazolin-2(1H)-one (0.12g, 0.25mmol) and methyl iodide (0.071g, 0.5mmol) were dissolved in 2ml of N,N-dimethylformamide and placed in an ice bath at 0°C Stir for 5min, add 60% sodium hydride (0.03g, 0.018mmol) in batches, continue to react in an ice bath for 2 hours, add 10ml of water, solids are precipitated, filter with suction, wash the filter cake with petroleum ether, and dry to obtain 6- (3,5-Dimethylisoxazole)-1-methyl-4-phenyl-3-((1-phenyl-1H-1,2,3-triazole)methyl)-3, 0.11 g of 4-dihydroquinazolin-2(1H)-one is a white solid with a yield of 89.05%. 1 HNMR (300MHz, DMSO) δ8.69(s, 1H), 7.86(d, J=7.9Hz, 2H), 7.58(t, J=7.7Hz, 2H), 7.48(d, J=7.1Hz, 1H) , 7.43-7.23(m, 7H), 7.08(d, J=8.3Hz, 1H), 5.80(s, 1H), 5.26(d, J=15.6Hz, 1H...

Embodiment 14

[0087] The synthetic route is:

[0088]

[0089] Reagents and conditions: a) ethyl azidoacetate, copper sulfate pentahydrate, sodium ascorbate, dichloromethane, methanol, water, room temperature; b) hydrated lithium hydroxide, methanol, water, room temperature; c) tetrahydropyrrole, O -Benzotriazole-tetramethyluronium hexafluorophosphate, diisopropylethylamine, N,N-dimethylformamide, room temperature; d) 3,5-dimethylisoxazole-4 - pinacol borate, [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium dichloromethane complex, potassium carbonate, toluene, methanol, N,N-dimethylformaldehyde Amide, nitrogen, 80°C.

[0090] a) Mix 6-bromo-4-phenyl-3-propynyl-3,4-dihydroquinazolin-2(1H)-one (0.25g, 0.73mmol) and ethyl azidoacetate (0.14g , 1.1mmol) was dissolved in the mixed solution of 3ml dichloromethane, 3ml methanol and 2ml water, stirred at room temperature, added copper sulfate pentahydrate (0.018g, 0.073mmol), stirred at room temperature for 20min, added sodium ascorbat...

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Abstract

The invention relates to a preparation method of triazole derivatives and medical application of the triazole derivatives. The invention particularly relates to triazole derivatives disclosed as general formula (I) and pharmaceutical salts thereof or a pharmaceutical composition containing the triazole derivatives or pharmaceutical salts thereof, and a preparation method thereof, and further relates to application of the triazole derivatives and pharmaceutical salts thereof or pharmaceutical composition containing the triazole derivatives and pharmaceutical salts thereof as a BET inhibitor in treating multiple tumors.

Description

technical field [0001] The invention relates to the field of drug synthesis, in particular, the invention relates to triazole compounds, their pharmaceutical compositions and their pharmaceutical use as BET inhibitors. Background technique [0002] Epigenetic phenomena include DNA modification, histone modification, chromatin remodeling, and non-coding RNA regulation (ncRNA), etc. Histone acetylation is the most studied histone modification method. Acetylation can neutralize the positive charge of lysine, weaken the affinity between DNA and histone, and make the chromatin structure loose and open, which is conducive to gene transcription , chromatin remodeling and DNA repair. In addition, acetyllysine can also provide a recognition and binding site for the histone acetyl recognizer containing the Bromodomain domain, which is beneficial for the recognizer to recruit related proteins and regulate gene transcription. [0003] In recent years, studies have found that BET famil...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D413/14A61P35/00A61P35/02
CPCC07D413/14
Inventor 张惠斌周金培赵雷磊张兵徐斌韩丽杨一飞
Owner CHINA PHARM UNIV
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