Benzoheterocycle substituted phenanthridine quaternary ammonium salt derivative as well as preparation method and application thereof

A technology of benzoheterocycle and derivatives, applied in the field of new pharmaceutical compounds, can solve problems such as insufficient druggability, and achieve the effects of good bactericidal effect, significant inhibitory effect, and significant interference effect

Active Publication Date: 2021-06-11
SHANDONG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] At present, according to the research of the inventors, the reported FtsZ inhibitors such as PC190723 Has excellent antibacterial activity, the compound is simplified from sanguinarine, with 3-methoxybenzamide (3-MBA) as the core structure, but its druggability is still insufficient

Method used

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  • Benzoheterocycle substituted phenanthridine quaternary ammonium salt derivative as well as preparation method and application thereof
  • Benzoheterocycle substituted phenanthridine quaternary ammonium salt derivative as well as preparation method and application thereof
  • Benzoheterocycle substituted phenanthridine quaternary ammonium salt derivative as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0054] Example 1 Synthesis of 6-bromoindole intermediate 1a

[0055]

[0056] Get 6-bromoindole (1.5g, 7.65mmol) and be dissolved in DMF, N 2 Under protection, NaH (0.37g, 9.25mmol) was added at 0°C, and after stirring for 30min, methyl iodide (15.3mmol) was added, transferred to room temperature and stirred for 2h, and the reaction was complete as detected by TLC. Ethyl acetate was added to the reaction solution, and saturated NH 4 Cl solution was washed three times, saturated NaCl solution was washed three times, and dried over anhydrous magnesium sulfate. Spin dry under reduced pressure and make sand. Silica gel column chromatography (pure PE as the eluent) gave 1a as a colorless oil with a yield of 93.1%.

Embodiment 2

[0057] Example 2 Synthesis of 4-(6'-indolyl) aniline intermediate 2a

[0058]

[0059] Get the product obtained in Example 1 (1.49g, 7.12mmol), and 4-aminophenylboronic acid pinacol ester (1.72g, 7.83mmol), be dissolved in 15ml of dioxane, get potassium carbonate (4.92g, 35.6mmol ) was dissolved in 15ml of water, added to the organic phase, and finally tetrakistriphenylphosphine palladium (cat.), N 2 Protected, heated to reflux at 101°C for 12h, TLC detected that the reaction was almost complete. The reaction solution was spin-dried to dry the organic phase, added an appropriate amount of ethyl acetate for extraction, separated to remove the water phase, washed the organic phase three times with saturated NaCl solution, and dried over anhydrous magnesium sulfate. Concentrate the organic phase, silica gel column chromatography (eluent PE:EA:Et 3 N=30:1:0.1→PE:EA:Et 3 N=3:1:0.1), and 2a was obtained as a yellow oil with a yield of 65.8%.

Embodiment 3

[0060] Example 3 Synthesis of 2-bromo-3-methylbenzoyl chloride intermediate 4l

[0061]

[0062] Take 3l of 2-bromo-3-methylbenzoic acid (1.5g, 6.98mmol), dissolve it in 8ml of thionyl chloride, heat and reflux at 78°C for 2h, and TLC detects that the reaction is complete. The reaction solution was spin-dried under reduced pressure to obtain a pale yellow oil, which was directly used in the next step without purification.

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PUM

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Abstract

The invention discloses a benzoheterocycle substituted phenanthridine quaternary ammonium salt derivative and a preparation method and application thereof, the benzoheterocycle substituted phenanthridine quaternary ammonium salt derivative has a structure shown as a formula (I), wherein R1 is selected from benzoheterocycle, substituted benzoheterocycle and aromatic heterocycle; R2 is selected from hydrogen, alkyl, cycloalkyl, heteroalkyl, alkoxy, halogen, cyano, amino, dimethylamino, nitryl, trifluoromethyl, trifluoromethoxy, acetamido and hydroxyl; x is halogen or benzenesulfonic acid anion. The derivative provided by the invention is completely different from a traditional 3-methoxybenzamide (3-MBA) mother nucleus in structure and has physicochemical properties different from those of the 3-MBA mother nucleus, and experiments show that the derivative has an effect of inhibiting FtsZ, can be used as an FtsZ inhibitor and can also be used as a bacteriostatic agent.

Description

technical field [0001] The invention belongs to the field of new pharmaceutical compounds, and relates to phenanthridine quaternary ammonium salt derivatives substituted by benzo heterocycles and their preparation methods and applications. Background technique [0002] The information disclosed in this background section is only intended to increase the understanding of the general background of the present invention, and is not necessarily taken as an acknowledgment or any form of suggestion that the information constitutes the prior art already known to those skilled in the art. [0003] The discovery of penicillin is a milestone in the history of antibacterial drug development. During World War II, penicillin first moved from the laboratory to the clinic, saving countless lives. Since then, the demand for antibacterial drugs has been increasing. In recent years, with the widespread use and even abuse of antimicrobials, an "artificial screening" of bacteria has been virtua...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D417/04C07D401/04A61K31/473A61P31/04
CPCC07D417/04C07D401/04A61P31/04Y02A50/30
Inventor 马淑涛张楠宋迪
Owner SHANDONG UNIV
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