Synthesis of dihydropyrazol sulfonamide derivatives containing benzodioxane skeletons and application of dihydropyrazol sulfonamide derivatives in anti-cancer drugs

A technology of dihydropyrazolesulfonamide and benzodioxane, which is applied in the synthesis of a class of dihydropyrazolesulfonamide derivatives containing benzodioxane skeleton and its application in anticancer drugs, can solve the problem of easy Problems such as drug resistance, application range limitation, and adverse reactions

Inactive Publication Date: 2014-12-24
NANJING UNIV
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  • Abstract
  • Description
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  • Application Information

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Problems solved by technology

[0002] Sulfonamides have a variety of biological activities and have always been a research hotspot in the field of medicinal chemistry. They are widely used in antibacterial, hypotensive, diuretic, etc. However, these drugs are bacteriostatic agents without bactericidal effect, and are prone to drug resistance Sexuality and frequent use will produce many adverse reactions, so its application range is greatly limited
However, due to its tendency to produce drug resistance, the scope of use has been gradually reduced

Method used

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  • Synthesis of dihydropyrazol sulfonamide derivatives containing benzodioxane skeletons and application of dihydropyrazol sulfonamide derivatives in anti-cancer drugs
  • Synthesis of dihydropyrazol sulfonamide derivatives containing benzodioxane skeletons and application of dihydropyrazol sulfonamide derivatives in anti-cancer drugs
  • Synthesis of dihydropyrazol sulfonamide derivatives containing benzodioxane skeletons and application of dihydropyrazol sulfonamide derivatives in anti-cancer drugs

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0014] Example 1: Preparation of 4-(5-(1.3-benzodioxane)-3-phenyl-4,5-dihydropyrazole)benzenesulfonamide (compound 39)

[0015]

[0016] Under stirring, 1,3-epoxybenzodioxanechalcone (1.0g, 3.87mmol), ethanol (25mL), p-hydrazinobenzenesulfonamide (0.97g, 5.03mmol), acetic acid (1.0mL ) into a 50mL round-bottomed flask, some solids were still insoluble; the flask was transferred to an oil bath, refluxed for 6h, and TLC tracked the reaction (developing agent V AcOEt :V 正己烷 =1:2), after the reaction was completed, filtered, the solid was washed with distilled water, and finally dried in vacuum, the obtained solid was dissolved in absolute ethanol for recrystallization and purification to obtain the crystalline target compound.

[0017] White crystals, yield 66.4%. m.p.212~214℃; 1 H NMR (DMSO-d6, 400MHz) δ: 7.80 (d, J=7.4Hz, 2H, ArH), 7.62 (d, J=8.6Hz, 2H, ArH), 7.48~7.40 (m, 3H, ArH), 7.11 (d, J=8.6Hz, 2H, ArH), 7.04 (s, 2H, NH 2 ), 6.87(d, J=7.9Hz, 1H, ArH), 6.78~6.75(m,...

Embodiment 2

[0018] Example 2: Preparation of 4-(5-(1.3-benzodioxane)-3-(m-methylphenyl-4,5-dihydropyrazole)benzenesulfonamide (compound 40)

[0019]

[0020] The preparation method is the same as in Example 1. White crystals were obtained with a yield of 75.8%. m.p.187~188℃; 1 H NMR (DMSO-d6, 400MHz) δ: 7.64~7.56 (m, 4H, ArH), 7.34 (t, J=7.6Hz, 1H, ArH), 7.23 (d, J=7.4Hz, 1H, ArH), 6.10 (d, J=8.6Hz, 2H, ArH), 7.04 (s, 2H, NH 2 ), 6.87(d, J=7.8Hz, 1H, ArH), 6.75(d, J=9.9Hz, 2H, ArH), 5.98(s, 2H, CH 2 ), 5.55 (dd, J 1 =4.7,J 2 = 4.8Hz, 1H, 5-H), 3.91(dd, J 1 =12.1,J 2 = 12.1Hz, 1H, 4-H b ), 3.17 (dd, J 1 =4.8,J 2 =4.7Hz, 1H, 4-Ha), 2.37(s, 3H, CH 3 ), .ESI-MS: 436.1 [M+H] + .Anal.Calcd for C 21 h 23 N 3 o 4 S: C, H, N.

Embodiment 3

[0021] Example 3: Preparation of 4-(5-(1.3-benzodioxane)-3-(m-methoxyphenyl-4,5-dihydropyrazole)benzenesulfonamide (compound 41)

[0022]

[0023] The preparation method is the same as in Example 1. White crystals were obtained with a yield of 76.6%. m.p.219~221℃; 1 H NMR (DMSO-d6, 400MHz) δ: 7.61 (d, J=8.7Hz, 2H, ArH), 7.37~6.99 (m, 8H, ArH), 6.87 (d, J=7.9Hz, 1H, ArH), 6.76 (s, 2H, NH 2 ), 6.00 (s, 2H, CH 2 ), 5.56 (dd, J 1 =4.9,J 2 =5.0Hz, 1H, 5-H), 3.91(dd, J 1 =12.2,J 2 =12.0Hz, 1H, 4-H b ), 3.82 (s, 3H, CH 3 ), 3.18 (dd, J 1 =5.0,J 2 = 4.8Hz, 1H, 4-Ha).ESI-MS: 452.1 [M+H] + .Anal.Calcd for C 21 h 23 N 3 o 5 S: C, H, N.

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Abstract

The invention relates to synthesis of dihydropyrazol sulfonamide derivatives containing benzodioxane skeletons. The synthesis is characterized by being provided with a general formula shown in descriptions. The dihydropyrazol sulfonamide derivatives containing the benzodioxane skeletons play an obvious role in inhibiting human mammary cancer cells (MCF-7), cervical carcinoma cells (HeLa), lung cancer cells (A549), liver cancer cells (HepG2) and matrix metalloproteinase-2 (MMP-2), and meanwhile, show cell toxicity, which is equivalent to or better than that of positive control drugs, to human kidney epithelial cells (293T). Thus, the dihydropyrazol sulfonamide derivatives containing the benzodioxane skeletons can be applied to the preparation of anti-tumor drugs. The invention discloses a preparation method and anti-tumor bioactivity of the dihydropyrazol sulfonamide derivatives containing the benzodioxane skeletons.

Description

Contents of the invention [0001] The object of the present invention is to provide a class of synthesis of dihydropyrazolesulfonamide derivatives containing benzodioxane skeleton and its application in anticancer drugs Background technique [0002] Sulfonamides have a variety of biological activities and have always been a research hotspot in the field of medicinal chemistry. They are widely used in antibacterial, hypotensive, diuretic, etc. However, these drugs are bacteriostatic agents without bactericidal effect, and are prone to drug resistance Sexuality and frequent use will produce many adverse reactions, so that its application range is greatly limited. However, due to its easy drug resistance, the scope of use has been gradually reduced. However, the literature in recent years has repeatedly reported that its derivatives have activities other than antibacterial, the most notable of which is antitumor activity. [0003] Pyrazoles are an important class of heterocycl...

Claims

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Application Information

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IPC IPC(8): C07D405/14C07D405/04A61K31/4155A61P35/00
CPCC07D405/04C07D405/14
Inventor 朱海亮严晓强邱寒月王鹏飞王忠长
Owner NANJING UNIV
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