Carbazole sulfonamide derivative and its preparation method

A technology for carbazole sulfonamide and derivatives, which is applied in the field of carbazole sulfonamide derivatives and their preparation, and can solve the problems of difficult synthesis, toxic side effects, poor bioavailability, etc.

Active Publication Date: 2010-05-05
SHANXI PUDE PHARMA CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the application and preparation of these drugs have the following problems: as a natural product of a macromolecule, it is very difficult to synthesize, has poor bioavailability, and has toxic side effects. In particular, the multidrug-resistant glycoprotein (P -gp), the effectiveness of its treatment has been seriously challenged (Li, Jian-Nong; Song, Dan-Qing; Lin, Yi-He; et al.Biochemical Pharmacology (2003), 65 (10), 1691-1699), which to some extent limited the development and use of paclitaxel and vinblastine-based tubulin inhibitors

Method used

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  • Carbazole sulfonamide derivative and its preparation method
  • Carbazole sulfonamide derivative and its preparation method
  • Carbazole sulfonamide derivative and its preparation method

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0132] Example 1: N-(3,4-dimethoxyphenyl)-9-ethylcarbazole-3-sulfonamide (42)

[0133] 9-ethylcarbazole-3-sulfonyl chloride was synthesized according to the method in Mitsumori, Susumu; Tsuri, Tatsuo; Honma, Tsunetoshi et al., Journal of Medicinal Chemistry (2003), 46(12), 2436-2445.

[0134] Add 3mlDMF and 3,4-dimethoxyaniline (80mg, 0.52mmol) to the reaction flask, add homemade 9-ethylcarbazole-3-sulfonyl chloride (150mg, 0.51mmol) while stirring at room temperature, and after 5 minutes , triethylamine (0.11ml, 0.77mmol) was added and the reaction was continued for 2 hours. Then, ice water was added, stirred for a while, the precipitate was filtered, washed with water three times, dried, and separated by VLC to obtain a light brown solid (160 mg, 76%), mp 175-177°C.

[0135] 1 H NMR (DMSO-d 6 ); δ1.30(t, J=7.2Hz, 3H), 3.59(s, 6H), 4.46(q, J=7.2Hz, 2H), 6.56(dd, J=8.7, 2.1Hz, 1H), 6.71 -6.74(m, 2H), 7.27(dd, J=7.5, 7.2Hz, 1H), 7.53(dd, J=7.8, 7.5Hz, 1H), 7.68(d, J=8.1Hz, ...

Embodiment 2

[0139]Example 2: N-(3,5-dimethoxyphenyl)-9-ethylcarbazole-3-sulfonamide (66)

[0140] The product is a light brown solid, yield: 63%; mp 171-173°C.

[0141] 1 H NMR (DMSO-d 6 ); δ1.30(t, J=6.9Hz, 3H), 3.60(s, 6H), 4.46(q, J=6.9Hz, 2H), 6.07(d, J=2.1Hz, 1H), 6.32(d , J=2.1Hz, 2H), 7.28(dd, J=7.5, 7.2Hz, 1H), 7.54(dd, J=7.8, 7.5Hz, 1H), 7.68(d, J=8.1Hz, 1H), 7.77 (d, J=8.7Hz, 1H), 7.85(d, J=8.7Hz, 1H), 8.28(d, J=7.5Hz, 1H), 8.66(s, 1H), 10.20(s, 1H).

[0142] 13 C NMR (DMSO-d 6 );

[0143] Elemental Analysis C 22 h 22 N 2 o 4 S, Calculated: C, 64.37; H, 5.41; N, 6.83. Found: C, 64.70; H, 5.67; N, 6.90.

Embodiment 3

[0144] Example 3: N-(3,4-methylenedioxyphenyl)-9-ethylcarbazole-3-sulfonamide (65)

[0145] The product is a light brown solid, yield: 74%; mp 182-184°C.

[0146] 1 H NMR (DMSO-d 6 ); δ1.30(t, J=6.9Hz, 3H), 4.46(q, J=6.9Hz, 2H), 5.89(s, 2H), 6.50(d, J=8.4Hz, 1H), 6.68-6.71 (m, 2H), 7.27(dd, J=7.5, 7.2Hz, 1H), 7.53(dd, J=7.8, 7.5Hz, 1H), 7.68(d, J=8.4Hz, 1H), 7.72-7.79( m, 2H), 8.25 (d, J = 7.8 Hz, 1H), 8.55 (s, 1H), 9.89 (s, 1H).

[0147] 13 C NMR (DMSO-d 6 );

[0148] Elemental Analysis C 21 h 18 N 2 o 4 S·0.3H 2 O, Calculated: C, 63.07; H, 4.70; N, 7.01. Found: C, 62.99; H, 4.33; N, 6.83.

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Abstract

The invention provides a new carbazole sulfonamide derivation and medicinal salt, comprising the general formula as follows (I). The compound can be small molecular microtubulin depressant which not only have the effect of antimicrocapillarity but also have the prominent antineoplastic activity, also the molecular weight is small, it is simple to synthesize and the toxic side effect is little. This invention also provides the medicinal compounds which contain the carbazole sulfonamide derivation as active constituent.

Description

technical field [0001] The invention relates to a novel carbazole sulfonamide derivative and a preparation method thereof, and also provides a pharmaceutical composition containing the carbazole sulfonamide derivative as an active ingredient. Background technique [0002] Tubulin inhibitors are a class of very effective antitumor drugs. With the widespread clinical application of paclitaxel (Paclitaxol and Docetaxol) and the in-depth understanding of the structure and function of microtubules, antitumor drugs targeting tubulin The research and development of tumor drugs has increasingly attracted the attention and interest of pharmaceutical companies and pharmacologists all over the world. [0003] Microtubules are the main components of the cytoskeleton, mainly assembled by α- and β-tubulin heterodimers. Microtubules are ubiquitous in eukaryotic cells and play an important role in maintaining cell shape, cell division and proliferation, organelle composition and transporta...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D209/84A61K31/403A61P35/00
CPCC07D409/12C07D401/12C07D405/12A61P35/00
Inventor 胡来兴大卫·W·博伊金王跃明李卓荣蒋建东
Owner SHANXI PUDE PHARMA CO LTD
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