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Sulfonamides as cccDNA inhibitors

A compound and selected technology, applied in the direction of amide active ingredients, organic chemistry, antiviral agents, etc., can solve the problems of inability to clear and easy to recur.

Active Publication Date: 2021-06-25
CHIA TAI TIANQING PHARMA GRP CO LTD +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] It is generally believed that neither alpha interferon nor lamivudine can clear intracellular HBV cccDNA, and HBV still has the ability to infect new liver cells during the treatment of these antiviral drugs, and these antiviral drugs are ineffective in clearing cccDNA, and it is easy to relapse after drug withdrawal , so long-term use of antiviral drugs is required for patients with chronic hepatitis B

Method used

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  • Sulfonamides as cccDNA inhibitors
  • Sulfonamides as cccDNA inhibitors
  • Sulfonamides as cccDNA inhibitors

Examples

Experimental program
Comparison scheme
Effect test

reference example 1

[0250] Reference Example 1: Synthesis of Compound BB-1

[0251]

[0252] synthetic route:

[0253]

[0254] Compound BB-1-1 (2.00g) was dissolved in pyridine (20.00mL), then compound BB-1-2 (2.16g) was added at 0°C, and the reaction solution was stirred at 0°C for 5 hours. The reaction was quenched with 2N hydrochloric acid at 0°C. The reaction solution was extracted with ethyl acetate (20 mL*3), the organic phases were combined, washed with brine (20 mL*2), dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to obtain a crude product. The crude product was subjected to flash preparative chromatography (petroleum ether: ethyl acetate = 20:1) to obtain the target compound BB-1 (yellow solid, 900 mg). MS (ESI) m / z: 392 [M+Na] + .

reference example 2

[0255] Reference Example 2: Synthesis of Compound BB-2

[0256]

[0257] synthetic route:

[0258]

[0259] Compound BB-2-1 (1.00g) and compound BB-2-2 (1.81g) were dissolved in N,N-dimethylformamide (50.00mL), and HATU (4.83g) was dissolved at 25°C and N,N-diisopropylethylamine (3.28 g) were added to the above reaction liquid, and stirred at 25° C. for 14 hours. The crude product was purified by flash chromatography (petroleum ether: ethyl acetate = 1:1) to obtain the target compound BB-2 (colorless oily liquid, 1.40 g). MS (ESI) m / z: 259 [M+H-tBu] + .

reference example 3

[0260] Reference Example 3: Synthesis of Compound BB-3

[0261]

[0262] synthetic route:

[0263]

[0264] Step 1: Synthesis of Compound BB-3-3

[0265] Compound BB-3-1 (1.00 g) was dissolved in dichloromethane (15.00 mL), and compound BB-3-2 (465.64 mg) was added, and the reaction solution was reacted at 15° C. for 1 hour. The reaction solution was concentrated to obtain a crude product. The crude product was dissolved in 15 mL of dichloromethane and separated by flash preparative chromatography (dichloromethane:methanol=gradient elution, from 1:0 to 10:1) to obtain the target compound BB-3-3 (white solid, 1.50 g). MS (ESI) m / z: 298 [M+H] + .

[0266] Step 2: Synthesis of Compound BB-3

[0267] Compound BB-3-3 (1.50 g) was dissolved in dichloromethane (5.00 mL), and hydrochloric acid in dioxane (4 mol / L, 5.62 mL) was added, and the mixture was reacted at 15° C. for 1.5 hours. The reaction solution was concentrated to obtain the target compound BB-3 (light yellow ...

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Abstract

A series of sulfonamide compounds as cccDNA inhibitors are provided, specifically, a compound represented by formula (I) or a pharmaceutically acceptable salt as cccDNA inhibitors is provided.

Description

[0001] References to related applications [0002] This application claims the rights and interests of the Chinese invention patent application with the application number CN201610980092.3 filed with the Intellectual Property Office of the People's Republic of China on November 08, 2016, which is incorporated by reference in its entirety into this application. technical field [0003] This application relates to a series of sulfonamide compounds as cccDNA inhibitors. Specifically, the present application relates to a compound of formula (I) or a pharmaceutically acceptable salt thereof as a cccDNA inhibitor. Background technique [0004] Hepatitis B virus (hepatitis B, HB) is caused by hepatitis B virus (hepatitis B virus, HBV). HBV infection can not only lead to acute and chronic viral hepatitis and severe hepatitis, but also closely related to the occurrence and development of liver cirrhosis (liver cirrhosis, LC) and hepatocellular carcinoma (hepatocellular carcinoma, HC...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D231/24C07D207/27C07D309/14A61P1/16A61P31/20A61K31/18
CPCA61K31/18A61P1/16A61P31/20C07D207/27C07D231/24C07D309/14
Inventor 付志飞张杨罗妙荣陈曙辉黎健徐宏江杨玲张喜全
Owner CHIA TAI TIANQING PHARMA GRP CO LTD