Coumarin esterified derivative with effect of inhibiting transcriptional activity of RXRalpha (Retinoid X Receptor) as well as preparation method and application of coumarin esterified derivative

A technology of derivatives and coumarin, applied in the field of coumarin esterification derivatives and preparation thereof, achieves the effects of short reaction time, less environmental pollution, and inhibition of RXRα transcriptional activity

Inactive Publication Date: 2017-08-25
XIAMEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

At present, there are no related reports on coumarin es

Method used

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  • Coumarin esterified derivative with effect of inhibiting transcriptional activity of RXRalpha (Retinoid X Receptor) as well as preparation method and application of coumarin esterified derivative
  • Coumarin esterified derivative with effect of inhibiting transcriptional activity of RXRalpha (Retinoid X Receptor) as well as preparation method and application of coumarin esterified derivative
  • Coumarin esterified derivative with effect of inhibiting transcriptional activity of RXRalpha (Retinoid X Receptor) as well as preparation method and application of coumarin esterified derivative

Examples

Experimental program
Comparison scheme
Effect test

Example Embodiment

[0031] Example 1: Preparation of 4-chloromethyl-7-hydroxycoumarin

[0032] Resorcinol (5.5g, 0.05mol), ethyl 4-chloroacetoacetate (9.9g, 0.06mol), and anhydrous bismuth chloride (0.8g, 2.5mmol) were mixed in a 100mL round-bottomed flask, and the The reaction was heated and stirred at 65 °C for 5 h under solvent conditions. After the reaction was completed, 16 mL of 50% ethanol aqueous solution was added, and the heating and stirring were continued at 65 °C for 10 min. g, namely 4-chloromethyl-7-hydroxycoumarin, with a yield of 70%.

[0033] NMR data for 4-chloromethyl-7-hydroxycoumarin:

[0034] 1 H NMR (400MHz, DMSO-d 6 ):δ4.95(s,2H,CH 2 Cl), 6.42(s, 1H, 3-H), 6.76(d, 1H, J=2.4Hz, 8-H), 6.83, 6.85(dd, 1H, J=2.4Hz, J=8.7Hz, 6- H),7.67(d,1H,J=8.7Hz,5-H),10.66(s,1H,OH)ppm

Example Embodiment

[0035] Example 2: Preparation of 4-chloromethyl-7-sorboyloxycoumarin (compound K1)

[0036] At 0°C, sorbic acid (0.224 g, 2.0 mmol) was placed in a 25 mL two-neck round-bottom flask, 2 drops of DMF were added dropwise, and 10 mL of anhydrous dichloromethane (CH 2 Cl 2 ) was dissolved, and oxalyl chloride (0.2 mL, 4.0 mmol) was added with a disposable syringe; one mouth of the two-necked round-bottomed flask was plugged with a rubber stopper, and the other mouth was connected to the exhaust gas absorption device; after the ice bath for 30 min, it gradually returned to room temperature, and at room temperature The reaction was stirred for 2h. After the reaction was completed, the unreacted oxalyl chloride was removed by distillation under reduced pressure to dryness; the product was treated with 2mL CH 2 Cl 2 After dissolution, it was added with a syringe to 10 mL of CH containing 4-chloromethyl-7-hydroxycoumarin (0.315 g, 1.5 mmol) and triethylamine (0.208 g, 1.8 mmol) 2 Cl ...

Example Embodiment

[0039] Example 3: Preparation of 4-chloromethyl-7-hexanoyloxycoumarin (compound K2)

[0040] At 0 °C, hexanoic acid (0.232 g, 2.0 mmol) was placed in a 25 mL two-neck round bottom flask, 2 drops of DMF were added dropwise, and 10 mL of CH was added 2 Cl 2 Dissolve, add oxalyl chloride (0.2mL, 4.0mmol) with a disposable syringe; one port of the two-necked round-bottomed flask is plugged with a rubber stopper, and the other port is connected to an exhaust gas absorption device; after ice bath for 30min, gradually return to room temperature, and stir at room temperature The reaction was carried out for 2h, after the reaction was completed, the unreacted oxalyl chloride was removed by distillation under reduced pressure to dryness; the product was treated with 2mL CH 2 Cl 2 After dissolution, it was added with a syringe to 10 mL of CH containing 4-chloromethyl-7-hydroxycoumarin (0.315 g, 1.5 mmol) and triethylamine (0.208 g, 1.8 mmol) 2 Cl 2 The mixture was reacted at room tempe...

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Abstract

The invention discloses a coumarin esterified derivative with an effect of inhibiting transcriptional activity of RXRalpha (Retinoid X Receptor) as well as a preparation method and application of the coumarin esterified derivative. The coumarin esterified derivative is a 4-chloromethyl-7-hydroxy coumarin esterified derivative shown by the following general formula. The invention also discloses a preparation method of the 4-chloromethyl-7-hydroxy coumarin esterified derivatives. The preparation method comprises the following steps: preparing 4-chloromethyl-7-hydroxy coumarin under solvent-free conditions by taking anhydrous bismuth chloride as a catalyst; preparing corresponding acyl chloride through different side chain acids; and reacting with the 4-chloromethyl-7-hydroxy coumarin, thereby obtaining the corresponding compound. The coumarin esterified derivative disclosed by the invention has a certain effect of inhibiting the transcriptional activity of RXRalpha and provides a thought for developing medicines taking the RXRalpha as a target. The structural formula is as shown in the specification.

Description

technical field [0001] The invention belongs to the field of medicinal chemistry, and in particular relates to a coumarin esterified derivative capable of inhibiting RXRα transcription activity, a preparation method and application thereof. Background technique [0002] Retinoid X Receptor (RXR) belongs to the superfamily of nonsteroidal hormone receptors and is a unique member of the nuclear receptor family with multiple biological functions, mediating many hormones, vitamin A and other drugs biological function. RXR is involved in the process of the body from embryonic development to organ formation, as well as the physiological regulation of various metabolisms in adults. In recent years, it has also been found that under the regulation of different ligands, RXR can perform nucleoplasmic shuttling and perform different biological functions, such as cell apoptosis, proliferation and differentiation. RXR includes three isoforms according to the promoter used and splicing ...

Claims

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Application Information

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IPC IPC(8): C07D311/16C07D405/12C07D407/12A61P35/00
CPCC07D311/16C07D405/12C07D407/12
Inventor 韩大雄王碧燕陈国旦王海燕
Owner XIAMEN UNIV
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