A kind of imidazo[4,5-f]o-1,10-phenanthroline derivative and its preparation method and application

A technology of o-phenanthroline and 5-f, which is applied in the direction of drug combination, organic chemistry, antineoplastic drugs, etc., to achieve the effect of inhibiting growth and reproduction, and the synthesis method is simple

A technology of o-phenanthroline and 5-f, which is applied in the direction of drug combination, organic chemistry, antineoplastic drugs, etc., to achieve the effect of inhibiting growth and reproduction, and the synthesis method is simple

CN102276607AInactive Publication Date: 2011-12-14SHANXI UNIV
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  • A kind of imidazo[4,5-f]o-1,10-phenanthroline derivative and its preparation method and application
  • A kind of imidazo[4,5-f]o-1,10-phenanthroline derivative and its preparation method and application
  • A kind of imidazo[4,5-f]o-1,10-phenanthroline derivative and its preparation method and application

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0023] Embodiment 1: Preparation of imidazo[4,5-f] and 1,10-phenanthroline derivatives

[0024] (1) (4g, 0.02mol) 1,10-phenanthroline and (4g, 0.03mol) KBr were slowly added successively in 30mL of concentrated sulfuric acid cooled and stirred in an ice bath, and 15mL of 86% to 97.5% mass concentration Add fuming nitric acid to the above solution, continue stirring in an ice bath for 30 minutes, and then heat to reflux for 5 hours. After the reaction, the liquid was poured into 320 g of ice water, neutralized with 10M NaOH, and then extracted with 50 mL×8 dichloromethane. The extract was dried with anhydrous sodium sulfate, filtered, and the solvent was evaporated to obtain the crude product of 1,10-phenanthroline-5,6-dione, which was recrystallized from methanol to obtain 1,10-phenanthroline-5, 6-diketone products;

[0025] (2) Add (0.26g, 1.25mmol) 1,10-phenanthroline-5,6-dione, (0.21g, 1.75mmol) p-hydroxybenzaldehyde and (1.92g, 25mmol) ammonium acetate to 3.5mL Glacial ...

Embodiment 2

[0033] Embodiment 2: Preparation of imidazo[4,5-f] and 1,10-phenanthroline derivatives

[0034] (1), (2) process is the same as embodiment 1

[0035] (3) Under nitrogen protection, (0.20g, 0.7mmol) p-hydroxybenzimidazol [4,5-f] o-phenanthroline compound and (0.18g, 4.7mmol) sodium hydride solution of mass concentration 25~50% In dried and degassed 20mL DMF, heat to 110°C and reflux for 60min; (0.52g, 2.8mmol) 1-(2-chloroethyl)piperidine hydrochloride was dissolved in dried and degassed 50mL DMF , This solution was added dropwise to the above-mentioned refluxing solution, and reacted at 110°C for 96h. After the reaction, it was cooled to room temperature, filtered, and the solvent was evaporated from the filtrate to obtain a solid. The solid was dissolved in methanol, adjusted to pH=7.0 with hydrochloric acid and triethylamine, the solvent was evaporated, and the obtained substance was separated by column chromatography, and the developing solvent was methanol: chloroform: gl...

Embodiment 3

[0042] Embodiment 3: Preparation of imidazo[4,5-f] and 1,10-phenanthroline derivatives

[0043] (1), (2) process is the same as embodiment 1

[0044] (3) Under nitrogen protection, (0.20g, 0.7mmol) p-hydroxybenzimidazol [4,5-f] o-phenanthroline compound and (0.13g, 3.4mmol) sodium hydride solution of mass concentration 25~50% In dried and degassed 20mL DMF, heat to 110°C and reflux for 40min; (0.60g, 3.5mmol) 1-(2-chloroethyl)pyrrole hydrochloride was dissolved in dried and degassed 50mL DMF, This solution was added dropwise to the above refluxing solution, and reacted at 110°C for 82h. After the reaction, it was cooled to room temperature, filtered, and the solvent was evaporated from the filtrate to obtain a solid. The solid was dissolved in methanol, adjusted to pH = 7.0 with hydrochloric acid and triethylamine, the solvent was evaporated, and the resulting substance was separated by column chromatography. The developing solvent was methanol: chloroform: glacial acetic ac...

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Abstract

The invention provides imidazole [4,5-f]-1,10-phenanthroline derivatives as well as a preparation method and application thereof. The method comprises the following steps: oxidizing 1,10-phenanthroline into 1,10-phenanthroline-5,6-diketone; forming p-hydroxy benzimidazole[4,5-f]phenanthroline with p-hydroxybenzaldehyde in ammonium acetate and glacial acetic acid condition; and forming the imidazole [4,5-f]-1,10-phenanthroline derivatives with 2-dimethylaminoethyl chloride hydrochloride or 1-(2-ethyl) piperidine hydrochloride or 1-(2-ethyl) pyrroline hydrochloride in anhydrous degasified DMF (dimethylformamide) containing NaH. The prepared imidazole [4,5-f]-1,10-phenanthroline derivatives can selectively identify and stabilize telomere G-tetrable helix DNA (deoxyribonucleic acid) in the existence of excessive double helix DNA, and can effectively inhibit growth and propagation of HeLa and HepG2 cancer cells, and can be used for preparing antitumor medicaments.

Description

technical field [0001] The present invention relates to heterocyclic compounds, in particular to an imidazo[4,5-f]o-1,10-phenanthroline derivative and its preparation method and use, especially the use as an antitumor drug. Background technique [0002] Telomere DNA is a non-coding, highly repetitive sequence, and its structure is mostly double-stranded except for the single-stranded region composed of many G bases at the 3' end. The repeat sequence of human telomere DNA is 5'-TTAGGG-3', about 3-6kb in length, and its 3'-end is a single-stranded region of 100-200 bases. Crystallographic and NMR studies have shown that these repetitive, G-rich sequences are at K + or Na + In the presence of it, it can fold into a G-quadruplex structure. [0003] The main function of telomeres is to prevent the deletion of base pairs at the end of chromosomes and end-to-end fusion during chromosome replication. In human cells, telomeric DNA suffers from an "end replication problem," in whi...

Claims

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Application Information

Patent Timeline
14 Dec 2011
Publication
CN102276607A
IPC
C07D471/14; A61P35/00
Inventors
魏春英; 王俊虹