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Synthesis method and anti-tumor application of a kind of phenanthridine derivatives

A synthesis method and derivative technology, which can be used in antitumor drugs, drug combinations, steroids, etc., and can solve the problems of poor water solubility, unfavorable research needs and clinical use, and low bioavailability.

Active Publication Date: 2021-01-05
GUILIN UNIVERSITY OF TECHNOLOGY +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The edema compound itself has poor water solubility, low bioavailability, low large-scale production efficiency, and high cost, which is not conducive to research needs and clinical use, and limits its further development

Method used

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  • Synthesis method and anti-tumor application of a kind of phenanthridine derivatives
  • Synthesis method and anti-tumor application of a kind of phenanthridine derivatives
  • Synthesis method and anti-tumor application of a kind of phenanthridine derivatives

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 18

[0045] Example 1.8, Preparation of 9-dimethoxy-5-(4-methoxybenzyl)-1,2,3,4-tetrahydrobenzo[c]phenanthridin-6-one (3)

[0046] 1) Preparation of intermediate (1)

[0047] Add 15 mL of thionyl chloride to 2-bromo-4,5-dimethoxybenzoic acid (1.50 g, 5.74 mmol), heat to reflux at 65° C. for 1 h, and remove the solvent by rotary evaporation to obtain acid chloride as a white solid. Dissolve m-aminoanisole (0.930g, 6.32mmol) in 3mL of dichloromethane, add 7mL of N,N-diisopropylethylamine and acid chloride dissolved in dichloromethane to it at 0°C (in 10min Added in 3 times), reacted for 1h and then transferred to room temperature and stirred for 1h. After the reaction was completed, quenched by adding 1M hydrochloric acid, extracted with dichloromethane, washed the organic phase with saturated sodium bicarbonate and saturated brine, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and separated by a column to obtain a white solid, namely 2- Bromo-4,5-dimeth...

Embodiment 28

[0052] Example 2.8, Preparation of 9-dimethoxy-1,2,3,4-tetrahydrobenzo[c]phenanthridine-6(5H)-one (4)

[0053] Take compound (3) (0.640g, 1.49mmol), add 2mL of trifluoroacetic acid, and heat to reflux at 75°C for 10h. Cool to room temperature after reaction finishes, add ethyl acetate, water to quench, ethyl acetate extracts, organic phase washes with water, saturated sodium bicarbonate washes, after anhydrous sodium sulfate is dried, with dichloromethane and ethyl acetate volume ratio 10: The eluent of 1 was subjected to column separation to obtain a white solid, which was 8,9-dimethoxy-1,2,3,4-tetrahydrobenzo[c]phenanthridin-6(5H)-one (4 ), yield: 75.6%. m.p.253.0~255.0℃; IR(KBr,cm -1 ):3439,3132,1651,1610,1496,1398,1234,1129,1079,836; 1 H-NMR (500MHz, CDCl 3 )δ8.56(s,1H),7.87(d,J=7.4Hz,2H),7.59(s,1H),7.03(d,J=8.3Hz,1H),4.10(s,3H),4.04( s,3H),2.88(t,J=6.1Hz,2H),2.77(t,J=6.4Hz,2H),2.51-2.47(m,1H),2.01-1.94(m,2H),1.88-1.81 (m,2H); 13 C-NMR (126MHz, CDCl 3 )δ153.79, 149...

Embodiment 3

[0054] Example 3. Preparation of 6-chloro-8,9-dimethoxy-1,2,3,4-tetrahydrobenzo[c]phenanthridine (5)

[0055] Put compound (4) (0.02mmol) into a reaction flask, add 40mL of phosphorus oxychloride, and heat to reflux at 105°C for 2h. Cool to room temperature after the reaction is over, carefully pour into a beaker with ice water, add concentrated ammonia dropwise until the pH is alkaline, filter the precipitate, wash the filter cake with water several times, and use petroleum ether and dichloromethane at a volume ratio of 1: 1 eluent for column separation to obtain a white solid, which is 6-chloro-8,9-dimethoxy-1,2,3,4-tetrahydrobenzo[c]phenanthridine (5), producing Rate: 84.8%. m.p.201.3~202.3℃; IR(KBr,cm -1 ):3434,3133,2928,1613,1578,1523,1501,1465,1402,1299,1249,1206,1160,1081,1043,953,840; 1 H-NMR (500MHz, CDCl 3 )δ8.13(d, J=8.4Hz, 1H), 7.83(s, 1H), 7.72(s, 1H), 7.35(d, J=8.5Hz, 1H), 4.14(s, 3H), 4.09( s,3H),3.35(t,J=6.1Hz,2H),2.96(t,J=6.0Hz,2H),1.93(ddd,J=17.9,10.9,5....

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Abstract

The invention belongs to the technical field of organic synthetic chemistry, and relates to the field of nitidine drugs, in particular to a synthetic method and anti-tumor application of a phenanthridine nitidine derivative. Experiments prove that the phenanthridine nitidine derivative has good anti-tumor activity, has obvious inhibition effect on HepG2, A549, H460 and CNE1 cancer cell strains, and can be used for researching preparation of anti-tumor drugs. In addition, the preparation method is mild in reaction condition and high in conversion ratio, and the universality of a substrate is wide.

Description

technical field [0001] The invention belongs to the technical field of organic synthesis, and in particular relates to a preparation method of phenanthridine-type dihedrine derivatives and its anti-tumor application. Background technique [0002] Zanthoxylum nitidum, also known as Zanthoxylum nitidum, is a vine of the Rutaceae Zanthoxylum nitidum. In my country, it is mainly distributed in Guangdong, Guangxi, Fujian and other places. Among them, Guangxi has the most abundant resources and is the authentic medicinal material producing area of ​​LMZ. The LMZ plant has the effects of promoting blood circulation and removing blood stasis, promoting qi and relieving pain, dispelling wind and dredging collaterals, detoxifying and reducing swelling. Folks are mainly used to treat bruises, stomach pain, toothache, rheumatic arthralgia, snake bites, burns and scalds. [0003] Nitidine is mainly extracted and isolated from the root of the plant. From the structural point of view, ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07J73/00C07D221/18A61P35/00
CPCA61P35/00C07D221/18C07J73/00Y02P20/55
Inventor 秦舒琴宋静茹李海云李典鹏
Owner GUILIN UNIVERSITY OF TECHNOLOGY