Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Isoniazid-indole heptamethine coupling compound and its preparation method and application

A kind of technology of indole heptamethine cyanine couple and compound, applied in the field of pharmacy

Active Publication Date: 2021-06-11
SHENYANG PHARMA UNIVERSITY
View PDF3 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In the prior art, there is no related report of connecting isoniazid and indole heptamethine through a hydrazone bond to obtain isoniazid-indole heptamethine coupling compound

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Isoniazid-indole heptamethine coupling compound and its preparation method and application
  • Isoniazid-indole heptamethine coupling compound and its preparation method and application
  • Isoniazid-indole heptamethine coupling compound and its preparation method and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0063] 2-[2-[[2-[4-[(2-Isonicotinoylhydrazone)phenoxy)-3-[2-[3,3-Dimethyl-1-(4-sulfonylbutyl Base)-2H-indol-2-yl]ethylidene]-1-cyclohexen-1-yl]vinyl]-3,3-dimethyl-1-(4-sulfobutyl) -Synthesis of 3H-indole ylide sodium salt (Z-1):

[0064] (1) Synthesis of 1-(4-sulfobutyl)-2,3,3-trimethyl-3H-indole ylide (compound 1-1)

[0065]

[0066] At room temperature, 2,3,3-trimethyl-3H-indole (5g, 31.4mmol) and 1,4-butyl sultone (12.82g, 94.3mmol) were added to a 250mL eggplant-shaped flask, Add 100mL o-dichlorobenzene, raise the temperature to 120°C, and react for 48h. After the reaction was completed, a brown-gray solid was obtained by cooling and suction filtration. After purification by silica gel column chromatography (dichloromethane:methanol=50:1), 6.34 g of a light gray solid was obtained, with a yield of 68.4%. MS(ESI)m / z:296.1[M+H] + .

[0067] (2) 2-[2-[[2-chloro-3-[2-[3,3-dimethyl-1-(4-sulfobutyl)-2H-indol-2-yl]ylidene Ethyl]-1-cyclohexen-1-yl]vinyl]-3,3-dimethyl-1-(4...

Embodiment 2

[0077] 2-[2-[[2-[4-(2-Isonicotinoylhydrazone)phenoxy)-3-[2-[3,3-Dimethyl-1-(5-carboxypentyl)- 2H-indol-2-yl]ethylidene]-1-cyclohexen-1-yl]vinyl]-3,3-dimethyl-1-(5-carboxypentyl)-3H-indole Synthesis of ylide bromide (Z-2):

[0078] (1) Preparation of 1-(5-carboxypentyl)-2,3,3-trimethyl-3H-indole ylide bromide (1-2)

[0079]

[0080] At room temperature, add 2,3,3-trimethyl-3H-indole (5g, 31.4mmol) and 6-bromohexanoic acid (18.29g, 94.3mmol) into a 500mL eggplant-shaped flask, add 150mL of acetonitrile, and heat up To 75°C, react for 72h. After the reaction, concentrate under reduced pressure to remove acetonitrile, add 500mL ethyl acetate and stir, and a brownish-red solid precipitates, which is filtered with suction, washed with ethyl acetate (200mL×2), filtered with suction, and dried in a vacuum oven to obtain a brownish-red solid. Red powdery solid 5.91g, yield 53.3%. MS(ESI)m / z:274.2[M-Br] + .

[0081] (2) 2-[2-[[2-chloro-3-[2-[3,3-dimethyl-1-(5-carboxypentyl)-2H-...

Embodiment 3

[0088] 2-[2-[[2-[4-(2-Isonicotinoylhydrazone)phenoxy)-3-[2-[3,3,5-trimethyl-1-(5-carboxypentyl) )-2H-indol-2-yl]ethylene]-1-cyclohexen-1-yl]vinyl]-3,3,5-trimethyl-1-(5-carboxypentyl)- Synthesis of 3H-indole ylide bromide (Z-3):

[0089]

[0090] Using the same preparation method as in Example 2, using 2,3,3,5-tetramethyl-3H-indole as a raw material, compound Z-3 was prepared through three steps of reaction. MS(ESI)m / z:916.50[M-Br] + ; 1 H NMR (600MHz, CD 3 OD)δ8.73(s,2H),8.32(s,1H),7.89(d,J=13.3Hz,5H),7.34-7.04(m,7H),6.12(d,J=14.0Hz,2H) ,4.05(s,4H),2.73(s,4H),2.34(s,6H),2.15(s,4H),2.10-1.98(m,3H),1.77(s,4H),1.64(s,5H ),1.42(s,5H),1.32(s,10H),1.22-1.09(m,2H); 13 C NMR (101MHz, CD 3 OD)δ173.25,164.51,163.99,163.12,151.10,150.96,142.64,142.37,141.42,136.59,131.46,130.21,129.85,124.00,123.21,122.44,116.41,111.80,100.96,66.87,50.52,50.18,49.64,49.43, 49.21, 49.00, 48.79, 48.57, 48.36, 45.11, 38.63, 28.33, 28.17, 27.85, 27.19, 25.21, 22.41, 21.34, 21.28, 15.44.

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention belongs to the technical field of medicine, and relates to a class of isoniazid-indole heptamethine coupling compound and its preparation and application. The invention adopts the combination principle to combine isoniazid with excellent in vivo fluorescence imaging characteristics and tumor targeting Functional indole heptamethine dyes are connected by hydrazone bonds to design a novel tumor-targeting isoniazid-indole heptamethine-isoniazid coupling compound, and its structural formula is shown in formula (I)-(III) , where R 1 , R 2 , R 3 , R 4 , m, n as described in the claims and specification. In vitro tumor cell growth inhibition test proves that the compound has good inhibitory effect on prostate tumor cells. The monoamine oxidase inhibitory activity test test shows that this type of compound has a moderate inhibitory effect on monoamine oxidase A, which is obviously stronger than isoniazid.

Description

technical field [0001] The invention belongs to the field of pharmacy, and relates to an isoniazid-indole heptamethine coupling compound and a preparation method and application thereof. It specifically relates to a hydrazone bond-linked monoamine oxidase inhibitor isoniazid-indole heptamethine coupling compound, a preparation method of the compound and an application in the preparation of antitumor drugs, especially the preparation of drugs for treating prostate tumors. Background technique [0002] Monoamine oxidase (Monoamine oxidase, MAO) is a flavoproteinase, mainly located in the outer mitochondrial membrane of the brain, liver, intestinal mucosa and other organs, has the function of regulating the concentration of amine in the organism, and plays an important role in the central nervous system and peripheral organs . [0003] True L et al. (True L, Coleman I, Hawley S, et al. A molecular correlate to the Gleason grading system for prostate adenocarcinoma[J]. Proc Nat...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Patents(China)
IPC IPC(8): C07D401/14A61K31/4439A61P35/00
CPCA61P35/00C07D401/14
Inventor 王钝杨晓光孔锐恒
Owner SHENYANG PHARMA UNIVERSITY
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com