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Azole and alcohol compounds based on coumarin and preparing method and application of azole and alcohol compounds

A compound and coumarin technology, applied in the field of chemistry, can solve the problems of narrow antibacterial spectrum, single dosage form, toxic and side effects, etc., and achieve the effects of simple preparation method, low cost, and easy availability of raw materials

Active Publication Date: 2016-06-22
SOUTHWEST UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0002] Bacterial and fungal infections are a common and highly-occurring infectious disease worldwide. Although many antibiotics and synthetic drugs have been used clinically, emerging pathogenic microorganisms, drug resistance of microorganisms and toxicity of clinical drugs Infectious diseases are still a fatal threat to human health due to the disadvantages of side effects, narrow antibacterial spectrum and single dosage form

Method used

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  • Azole and alcohol compounds based on coumarin and preparing method and application of azole and alcohol compounds
  • Azole and alcohol compounds based on coumarin and preparing method and application of azole and alcohol compounds
  • Azole and alcohol compounds based on coumarin and preparing method and application of azole and alcohol compounds

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0044] Embodiment 1, the preparation of compound I-1

[0045]

[0046] In a 50mL round bottom flask, intermediate III (1equiv) and sodium bicarbonate (1.5equiv) were mixed with ethanol (15mL) as a solvent, stirred at 60°C for 2h, cooled to room temperature, added epoxide V (1equiv), and heated The reaction was stirred at 70°C, and the reaction was followed by thin-layer chromatography until the end of the reaction, and then concentrated, extracted, separated by column chromatography, and dried to obtain a yellow solid with a yield of 72%.

[0047]

[0048] Among them, X 1 is fluorine, X 2 is 4-fluoro, and Im is benzimidazole.

[0049] Compound I-1: Melting point: 120–122°C; IR (KBr): 3432, 2926, 2853, 2823, 2378, 1721, 1695, 1616, 1511, 1459, 1332, 1218, 1139, 1013cm -1 ; 1 HNMR (600MHz, CDCl 3)δ9.76(s,1H),8.61(s,1H),7.96(s,1H),7.71(d,J=7.9Hz,1H),7.53(dd,J=15.6,8.9Hz,1H), 7.47(d,J=7.6Hz,1H),7.43–7.41(m,2H),7.31–7.29(m,2H),7.27–7.25(m,1H),7.21(t,J=7.5Hz,1H) ,6.83–6...

Embodiment 2

[0050] Embodiment 2, the preparation of compound 1-2

[0051]

[0052] In a 50mL round bottom flask, intermediate III (1equiv) and sodium bicarbonate (1.5equiv) were mixed with ethanol (15mL) as solvent, stirred at 60°C for 2h, cooled to room temperature, added epoxide V (1equiv), and heated Stir the reaction at 70°C, track the reaction by thin layer chromatography until the end of the reaction, then concentrate, extract, separate by column chromatography, and dry to obtain a yellow solid with a yield of 74%.

[0053]

[0054] Among them, X 1 is fluorine, X 2 is 4-fluoro, and Im is 5,6-dimethylbenzimidazole.

[0055] Compound I-2: Melting point: 127–129°C; IR (KBr): 3431, 2927, 2823, 2050, 1721, 1695, 1625, 1510, 1460, 1330, 1162, 1138, 1014cm -1 ; 1 HNMR (600MHz, CDCl 3 )δ9.77(s,1H),8.60(s,1H),7.84(s,1H),7.57(dd,J=15.6,8.9Hz,1H),7.47(d,J=5.8Hz,2H), 7.44–7.40(m,1H),7.30(d,J=8.3Hz,1H),7.29–7.25(m,1H),7.16(s,1H),6.84–6.79(m,1H),6.79–6.74( m,1H),5.10(s,1H),4.33(bs,2H...

Embodiment 3

[0056] Embodiment 3, the preparation of compound 1-3

[0057]

[0058] In a 50mL round bottom flask, intermediate III (1equiv) and sodium bicarbonate (1.5equiv) were mixed with ethanol (15mL) as solvent, stirred at 60°C for 2h, cooled to room temperature, added epoxide V (1equiv), and heated The reaction was stirred at 70°C, and the reaction was followed by thin-layer chromatography until the end of the reaction, and then concentrated, extracted, separated by column chromatography, and dried to obtain a yellow solid with a yield of 61%.

[0059]

[0060] Among them, X 1 is fluorine, X 2 is 4-fluoro, and Im is 2-methylbenzimidazole.

[0061] Compound I-3: Melting point: 105–107°C; IR (KBr): 3471, 2919, 2855, 1982, 1721, 1692, 1625, 1511, 1495, 1371, 1222, 1015cm -1 ; 1 HNMR (600MHz, CDCl 3 )δ9.76(s,1H),8.61(s,1H),7.71–7.64(m,2H),7.48(d,J=7.7Hz,1H),7.44–7.40(m,2H),7.32(d ,J=8.3Hz,1H),7.29(d,J=7.6Hz,1H),7.23–7.21(m,2H),6.88–6.85(m,2H),4.98(s,1H),4.44(d, J=15.2Hz, 1H)...

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Abstract

The invention discloses azole and alcohol compounds based on coumarin and further discloses a preparing method of the azole and alcohol compounds. The azole and alcohol compounds are shown in the general formula I and the general formula II. Substituted phenols serve as raw materials, amino-substituted or hydroxyl-substituted coumarin rings are obtained through multiple steps of reactions, and are then reacted with chloroacetyl chloride or phosphorus oxychloride to obtain a coumarin-containing derivative, the coumarin-containing derivative is reacted with piperazine in an acetonitrile alkaline solution to prepare a key intermediate, the intermediate is subjected to an ring-opening reaction with epoxide in an alkaline alcohol solution, and the azole and alcohol compounds shown in the general formula I and the general formula II can be prepared. The azole and alcohol compounds based on coumarin have certain inhibitory activity on tested bacteria / fungi, and can be used for preparing potential bacterium and / or fungus resisting medicine. R1, R2, R3, R4, X1, X2 and Im in the molecular formulas are defined in the claims.

Description

technical field [0001] The invention belongs to the field of chemistry, and in particular relates to a new class of coumarin-based azole alcohol compounds, a preparation method of the compound and its medical application. Background technique [0002] Bacterial and fungal infections are a common and highly-occurring infectious disease worldwide. Although many antibiotics and synthetic drugs have been used clinically, emerging pathogenic microorganisms, drug resistance of microorganisms and toxicity of clinical drugs The disadvantages of side effects, narrow antibacterial spectrum and single dosage form make infectious diseases still a fatal threat to human health. In view of this, the research and development of new anti-infective drugs is imminent. Coumarin is a class of compounds with α-benzopyrone structure, which is easy to be modified and introduced into various functional groups, and is playing an increasingly important role in the field of pharmacy. [0003] Azole a...

Claims

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Application Information

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IPC IPC(8): C07D405/12A61P31/04A61P31/10
CPCC07D405/12Y02A50/30
Inventor 周成合阿乌拉·斯里尼瓦萨·拉奥彭莘媚
Owner SOUTHWEST UNIVERSITY