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Novel sulfamide compound, and preparation method and application thereof

A technology of sulfonamides and compounds, applied in the field of medicinal chemistry

Active Publication Date: 2018-01-19
FOSHAN UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, due to the high mutation rate of HIV, drug resistance is still a major problem in the treatment of this virus. Therefore, it is still urgent to develop new protease inhibitors to overcome a series of problems of existing HIV-1 protease inhibitors. Therefore, the design and synthesis of new protease inhibitors is currently a hot spot in the field of new AIDS drug research and development.

Method used

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  • Novel sulfamide compound, and preparation method and application thereof
  • Novel sulfamide compound, and preparation method and application thereof
  • Novel sulfamide compound, and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0061] A kind of preparation method of novel sulfonamide compound, comprises the following steps:

[0062] (1) Add 300mg of NaBH 4 Add it into 10mL of ethylene glycol dimethyl ether and stir evenly, then control its temperature at -5°C to obtain liquid A;

[0063] (2) Add 1.9 g of methanesulfonic acid into 1 mL of ethylene glycol dimethyl ether and stir evenly to obtain liquid B;

[0064] (3) Slowly add liquid B to liquid A and stir evenly, while controlling the temperature at -5°C to obtain mixed liquid C;

[0065] (4) Add 1.2g of compound 6 and 1.4mL of isopropanol (i-PrOH) into 2.7mL of ethylene glycol dimethyl ether and stir evenly to obtain D mixture;

[0066] (5) Slowly add D mixture to C mixture, and control the temperature at -5°C, stir for 12h, then slowly add 1.2mL of triethanolamine while keeping the temperature at -5°C, and stir at -5°C for 30 After 1 min, slowly add 1.8 mL of NaBH containing 250 mg 4 Dimethylacetamide solution to obtain E mixed solution;

[0...

Embodiment 2

[0072] A kind of preparation method of novel sulfonamide compound, comprises the following steps:

[0073] (1) Add 300mg of NaBH 4 Add it into 10mL of ethylene glycol dimethyl ether and stir evenly, then control its temperature at -5°C to obtain liquid A;

[0074] (2) Add 1.9 g of methanesulfonic acid into 1 mL of ethylene glycol dimethyl ether and stir evenly to obtain liquid B;

[0075] (3) Slowly add liquid B to liquid A and stir evenly, while controlling the temperature at -5°C to obtain mixed liquid C;

[0076] (4) Add 1.2g of compound 8 and 1.4mL of isopropanol (i-PrOH) into 2.7mL of ethylene glycol dimethyl ether and stir evenly to obtain D mixture;

[0077] (5) Slowly add D mixture to C mixture, and control the temperature at -5°C, stir for 12h, then slowly add 1.2mL of triethanolamine while keeping the temperature at -5°C, and stir at -5°C for 30 After 1 min, slowly add 1.8 mL of NaBH containing 250 mg 4 Dimethylacetamide solution to obtain E mixed solution;

[0...

Embodiment 3

[0083] Same as Example 2, except that compound 3 was obtained after deprotecting the amine group and amido group of compound 22.

[0084] 15 mg of compound 22 in Example 2 was mixed with 9:1 trifluoroacetic acid (TFA):CH 2 Cl 2 Treat for 30 minutes, remove the solvent by co-evaporation with toluene, and under nitrogen, the resulting residue is mixed with N-benzenesulfonyl valine in tetramethylurea tetrafluoroborate, triethylamine and dimethylformamide The solution was reacted at room temperature for 10 h to obtain compound 3, which was confirmed to be the structure by LCMS detection.

[0085] The inhibitory activity of heterocyclic arylsulfonamide derivatives: compound 3, compound 4, compound 5 and compound 23a, compound 23b and compound 23c against HIV protease was determined using in vitro enzyme assay and intracellular assay, see Table 1. Interestingly, the most potent analog was found to be compound 3 (Ki = 0.6 nM). Replacing the C5 benzyl ring with an ethyl group did n...

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Abstract

The invention discloses a novel sulfamide compound, and a preparation method and application thereof. The preparation method of the novel sulfamide compound comprises the following steps: performing reaction on a compound 6 to generate a compound 9, obtaining a compound 12 by the compound 9, obtaining a compound 15 by the compound 12, obtaining a compound 21 by the compound 15, and obtaining a compound 4 by the compound 21; performing reaction on a compound 8 to generate a compound 11, obtaining a compound 14 by the compound 11, obtaining a compound 17 by the compound 14, obtaining a compound22 by the compound 17, and obtaining a compound 5 by the compound 22. Optionally, the compound 22 is subjected to reaction to generate a compound 3. The novel sulfamide compound can serve as an HIV-1protease inhibitor.

Description

technical field [0001] The invention belongs to the technical field of medicinal chemistry, and in particular relates to a novel sulfonamide compound and its preparation method and application. Background technique [0002] Because HIV-1 protease plays an important role in HIV virus replication, HIV-1 protease is the main target of AIDS drug therapy. Several protease inhibitors such as Lopinavir and Tipranavir have been shown to have potent inhibitory activity against HIV virus. However, due to the high mutation rate of HIV, drug resistance is still a major problem in the treatment of this virus. Therefore, it is still urgent to develop new protease inhibitors to overcome a series of problems of existing HIV-1 protease inhibitors. Therefore, the design and synthesis of new protease inhibitors is a hot spot in the field of new AIDS drug research and development. Contents of the invention [0003] Aiming at the problems existing in the prior art, the invention provides nov...

Claims

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Application Information

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IPC IPC(8): C07D213/71C07C311/19C07C303/40A61P31/18C07D409/04C07D261/08C07D231/12
Inventor 丁毅力李紫元王丙云
Owner FOSHAN UNIVERSITY