Nucleoside compound and application thereof in treating feline infectious peritonitis

A compound and drug technology, applied to nucleoside compounds and their application in the treatment of feline infectious peritonitis, can solve the problems of large side effects and can not reduce the high fatality rate of the disease and the like

Pending Publication Date: 2022-07-19
SUZHOU VIGONVITA LIFE SCIENCES CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] At present, the treatment of feline infectious peritonitis mainly uses immunomodulators, immunosuppressants and antiviral drugs for symptomatic treatment. These drugs have relatively large side effects and cannot reduce the high fatality rate of the disease

Method used

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  • Nucleoside compound and application thereof in treating feline infectious peritonitis
  • Nucleoside compound and application thereof in treating feline infectious peritonitis
  • Nucleoside compound and application thereof in treating feline infectious peritonitis

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0056] Example 1: Preparation of Compound 32:

[0057]

[0058] Step 1: 1.32 g of tert-butoxyacetic acid and 0.84 g of sodium bicarbonate were added to 30 mL of DMSO, and stirred at room temperature for 20 min until dissolved. 2.0 g of raw material A1 was added at room temperature, and the temperature was increased to 65° C. to react overnight. The raw material disappeared and the product was formed. The reaction was stopped, extracted with EA / water until the aqueous layer was substantially free of product, the organic phase was washed with saturated brine, dried and concentrated on the column, eluted with DCM / MeOH=30 / 1 to obtain 1.1 g of white solid B1.

[0059] 1 H NMR (400MHz, DMSO-d 6)δ8.05–7.86(m,3H),6.92(d,J=4.4Hz,1H),6.82(d,J=4.4Hz,1H),6.36(d,J=6.0Hz,1H),5.42( d, J=5.8Hz, 1H), 4.68(t, J=5.4Hz, 1H), 4.38(d, J=9.8Hz, 1H), 4.28–4.14(m, 2H), 4.00(s, 2H), 3.96–3.89(m, 1H), 1.12(s, 9H).

[0060] Step 2: 500 mg of the starting compound B1 was dissolved in 10 mL of DCM,...

Embodiment 2

[0086] Example 2: Solubility Test

[0087] Experimental method: refer to high performance liquid chromatography (Chinese Pharmacopoeia 2020 edition of the four general rules 0512).

[0088] a. Take about 1-2 mg of the compound, put it in a 10 ml volumetric flask, add 1 ml of water, shake vigorously for 30 seconds every 5 minutes, observe for 30 minutes, the sample is not completely dissolved, filter through a 0.45 μm filter membrane, and take the continuous filtrate as Test solution.

[0089] b. Take another appropriate amount of reference substance, dissolve in solvent (DMSO:methanol=10:90) and quantitatively dilute to make a solution containing 0.1mg per 1ml, as reference substance solution.

[0090] c. Precisely measure 20 μl of the reference substance and the test solution, respectively, inject them into the liquid chromatograph, and calculate the peak area according to the external standard method. The data obtained are shown in Table 2. Calculation formula: In the fo...

Embodiment 3

[0097] Example 3: Efficacy test of compounds 1, 32 and 85 on feline infectious peritonitis

[0098] experimental method:

[0099] 15 mg of compounds 1, 32, and 85 were dissolved in 5 mL of a solution (water:propylene glycol:PEG=2:1:1), respectively, to prepare an injection solution and administered by injection. The injection solution can be stored at room temperature. Use a 2mL disposable veterinary syringe to draw the corresponding volume of the injection solution and remove the air upwards. When injecting, choose a place with soft skin, loose subcutaneous tissue and less blood vessels, such as subcutaneous injection in the neck or medial thigh. The dosage is 2mg / Kg body weight once a day, blood is collected every three days and blood routine and corresponding biochemical index determination are carried out. For each compound, 15 cats with confirmed feline infectious peritonitis were tested.

[0100]figure 1 Shows the body weight changes of 15 cats in each of the 3 groups...

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PUM

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Abstract

The invention relates to a nucleoside compound and application of the nucleoside compound in treatment of feline infectious peritonitis. The compound belongs to a GS-441524 analogue. The compound has a very small toxic effect on normal cells of cats, and has an obvious inhibition effect on feline coronavirus. The compound can be used for preparing a feline coronavirus inhibitor, is used for treating feline infectious peritonitis, has the advantages of good curative effect, high safety and the like, and is very good in water solubility and easier to absorb.

Description

[0001] Related applications [0002] This application claims the priority of the Chinese patent application filed on April 23, 2021, the application number is CN202110442975.X, and the title is "a nucleoside compound and its application in the treatment of feline infectious peritonitis", hereby It is incorporated by reference in its entirety. technical field [0003] The present invention relates to a nucleoside compound and its application in treating cat infectious peritonitis. Background technique [0004] Feline infectious peritonitis (FIP) is a disease caused by infection with feline coronavirus. It is a chronic, progressive and fatal infectious disease. The disease is commonly found in two clinical forms, one is peritonitis. , Exudative type characterized by a large amount of ascites, that is, wet infectious peritonitis. One is dry infectious peritonitis characterized by uveitis such as obvious fibrin clots and retinal hemorrhages in the eyes without obvious symptom ...

Claims

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Application Information

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IPC IPC(8): C07D487/04A61K31/53A61K31/5377A61P31/14A61P29/00
CPCC07D487/04A61P31/14A61P29/00C07B2200/07
Inventor 雷洋曹刚胡榕
Owner SUZHOU VIGONVITA LIFE SCIENCES CO LTD
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