5-oxygen-substituted benzene alkene propionyl quinic acid compounds and medicine uses thereof

A technology of phenylacryloyl and quinic acid, which is applied in the field of 5-oxy-[3-substituted phenylacryloyl] quinic acid compounds and their preparation, and can solve problems such as side effects and the like

Inactive Publication Date: 2008-10-29
WENZHOU MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The clinical efficiency of interferon is only 30-50%, and it has the same side effects as nucleosides

Method used

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  • 5-oxygen-substituted benzene alkene propionyl quinic acid compounds and medicine uses thereof
  • 5-oxygen-substituted benzene alkene propionyl quinic acid compounds and medicine uses thereof
  • 5-oxygen-substituted benzene alkene propionyl quinic acid compounds and medicine uses thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0021] Example 1 : Compound I-a is the preparation of 5-oxo-[3-(4-methoxyphenyl) acryloyl]-quinic acid

[0022] Add p-methoxyphenylpropenic acid (103 mg, 0.58 mmol), carbonyldiimidazole (119 mg, 0.58 mmol) and 8 ml of tetrahydrofuran in the reaction flask, reflux for 2 hours, then add quinic acid (90 mg, 0.47 mmol), 1,8-diazabicyclo[5,4,0]11-alk-7-ene (DBU, 90 mg, 0.58 mmol), and the whole solution was refluxed for another 8 hours. Precipitation gave a pale yellow viscous solid, which was separated by reverse phase silica gel RP-18 column chromatography (methanol / water: 50 / 50) to obtain 43 mg of white solid with a yield of 26.7%.

[0023] Melting point: 122~124℃, R f (chloroform / methanol / formic acid: 50 / 2 / 1): 0.35; H NMR spectrum ( 1 HNMR, 400MHz, deuterated methanol): δ2.16~2.36 (4H, multiplet), 3.83 (3H, singlet), 4.26 (1H, double doublet), 4.55 (1H, multiplet), 4.98 (1H, doublet), 6.35 (1H, doublet), 6.82 (2H, singlet), 7.27 (2H, singlet), 7.69 (1H, doublet).

Embodiment 2

[0024] Example 2 : Compound I-a is the preparation of 5-oxo-[3-(4-methoxyphenyl) acryloyl]-quinic acid

[0025]

[0026] Add p-methoxyphenylacrylate (87 mg, 0.49 mmol), dicyclohexylcarbodiimide (100 mg, 0.49 mmol) and 8 ml of dichloromethane into the reaction flask, and stir at room temperature for 20 minutes , add quinic acid (75 mg, 0.39 mmol), 4-dimethylaminopyridine (DMAP, 10 mg, 0.049 mmol), the whole solution was reacted overnight at room temperature, and the insoluble matter was removed by suction filtration, the solvent was evaporated, and the Dissolved to obtain a white solid, which was separated by reverse-phase silica gel RP-18 column chromatography (methanol / water: 50 / 50) to obtain 38 mg of white solid with a yield of 28.6%.

Embodiment 3-8

[0027] According to the same method as in Example 2, the compounds of Example 3-8 shown in Table 1 were prepared:

[0028]

[0029] Table I

[0030]

[0031]

[0032] List the physicochemical data of each compound in Table 1 below:

[0033] Compound I-b: white solid, melting point: 132-135°C, R f (chloroform / methanol / formic acid: 50 / 2 / 1): 0.23; H NMR spectrum ( 1 HNMR) (400MHz, deuterated methanol): δ2.09~2.28 (4H, multiplet), 3.93 (1H, double doublet), 4.09 (1H, multiplet), 4.93 (1H, double doublet), 6.28( 1H, bimodal), 7.32 (1H, multiplet), 7.49 (1H, bimodal), 7.56 (1H, unimodal), 7.92 (1H, bimodal).

[0034] Compound I-c: white solid, melting point: 110-113°C, R f (chloroform / methanol / formic acid: 50 / 2 / 1): 0.38; H NMR spectrum ( 1HNMR) (400MHz, deuterated methanol): δ2.16~2.36 (4H, multiplet), 3.48 (3H, singlet), 3.51 (3H, singlet), 3.78 (1H, double doublet), 4.10 (1H , multiplet), 4.93 (1H, double doublet), 5.18 (2H, singlet), 5.26 (2H, singlet), 6.37 (1H, d...

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Abstract

The invention relates to 5-o-substitued phenyl propionyl quinic acid compounds and pharmaceutical application thereof, specifically 5-o-[3-substitued phenyl propionyl] quinic acid compounds having the formula of (I) and anti-hepatitis B virus activity and pharmaceutical salts thereof. The invention also relates to a preparation method of the quinic acid compounds, pharmaceutical application thereof, and drugs and pharmaceutical compositions containing the quinic acid compounds. The compounds having the formula of (I) and pharmaceutical salts thereof inhibit hepatitis B virus DNA (HBVDNA) replication and reduces hepatits B virus surface antigen (HBsAg) expression thereby to have prospect pharmaceutical application in the preparation of a drug for treating correlated hepatitis B virus infectious disease.

Description

technical field [0001] The present invention relates to the fields of organic chemistry, medicinal chemistry and pharmacology, in particular, the present invention relates to 5-oxo-[3-substituted phenylacryl]quinic acid compounds and their preparation methods, which are found to have Inhibit the replication of hepatitis B virus DNA (HBVDNA) and reduce the expression of hepatitis B virus surface antigen (HBsAg). The compounds and their pharmaceutically acceptable salts can be expected to be used in the preparation of medicines for treating related hepatitis B virus infectious diseases. Background technique [0002] From the first day of understanding viruses, human beings have been constantly looking for effective weapons against viruses, but there is still a lack of specific drugs for the treatment of viral diseases. Commonly used drugs in clinical practice include the following categories: 1. Antiviral drugs that inhibit virus replication; 2. Immunomodulatory drugs that en...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C69/736C07C69/65C07C69/618A61K31/216A61P1/16A61P31/12
Inventor 黄可新熊伟胡利红韩方方白骅于荣敏郝小江赵昱巫秀美李校堃瞿佳
Owner WENZHOU MEDICAL UNIV
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