Phenanthroindolizidine compound and NF kB inhibitor containing same as active ingredient

A technology of active ingredients and compounds, which is applied in the field of novel phenanthrene indolizidine alkaloid compounds or their salts, can solve the problems of strong cytotoxicity and heterogeneity, achieve excellent solubility, small side effects, and excellent NFκB inhibitory effect Effect

Inactive Publication Date: 2015-11-11
YAKULT HONSHA KK
View PDF2 Cites 2 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In addition, it is also known that sierphine exhibits strong cytotoxicity, and studies on the synthesis method are also being vigorously carried out (Non-Patent Document 13)
In addition, among the phenanthrene indolizidine alkaloids, it is known that isosilphine represented by the following formula (B) has central nervous system toxicity (Non-Patent Document 14)
In addition, in recent years, it has been known that sylphenine analogues represented by the following formulas (C) and (D) have shown strong cytotoxicity throughout the NCI60 cancer type panel test, and their mechanism of action is different from that of existing anticancer drugs. Tumor agents are different (Non-Patent Document 15)
In addition, it is known that a compound represented by the following formula (E), which is an insect-derived phenanthrene indolizidine alkaloid, has strong cytotoxicity (Non-Patent Document 16)

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
  • Phenanthroindolizidine compound and NF kB inhibitor containing same as active ingredient
  • Phenanthroindolizidine compound and NF kB inhibitor containing same as active ingredient
  • Phenanthroindolizidine compound and NF kB inhibitor containing same as active ingredient

Examples

Experimental program
Comparison scheme
Effect test

Embodiment

[0149] Hereinafter, examples are shown and the present invention will be described in more detail, but the present invention is not limited thereto.

[0150] The phenanthrene indolizidine alkaloid of the present invention is synthesized according to the reaction pathway of the following steps 1-10. When the substituent represented by R needs to be protected, an appropriate protecting group is used for the reaction.

[0151]

Synthetic example 1

[0153] Synthetic R 1 ~R 6 Compounds represented by the following groups. The operations of Steps 1 to 10 are shown below.

[0154] Compound 1

[0155] R 1

R 2

R 3

R 4

R 5

R 6

H

Oh

H

OCH 3

OCH 3

OCH 3

[0156] Step 1: Synthesis of stilbene

[0157] In an eggplant-shaped flask, in 3,4,5-trimethoxyphenylacetonitrile 5.0g (24.1mmol) and 4-hydroxybenzaldehyde 5.1g (24.1mmol, 1.0eq.) in ethanol 150mL suspension, under argon In an air atmosphere, 160 mg (2.4 mmol, 0.1 eq.) of sodium ethoxide was added with stirring at room temperature, and heated to reflux (oil bath temperature: 85° C.). After 3 hours, the disappearance of the raw material was confirmed, and the reaction liquid was cooled with an ice bath. The precipitated solid was suction-filtered with a Buchner funnel and a suction filter flask, and washed with 100 mL of methanol (twice). Drying was carried out at 60° C. under reduced pressure to obtain 9....

Synthetic example 2

[0189] Synthetic R 1 ~R 6 Compounds represented by the following groups. The operations and the yield of each operation are shown below.

[0190] [Table 2]

[0191] Compound 3

[0192] R 1

R 2

R 3

R 4

R 5

R 6

H

Oh

H

H

H

H

[0193] Process 1

[0194] Yield: 92.0%

[0195] 1 HNMR (400MHz, CDCl 3 )δ: 5.14 (2H, s), 7.02-7.08 (2H, m), 7.32-7.48 (9H, m), 7.62-7.68 (2H, m), 7.85-7.92 (2H, m)

[0196] Process 2

[0197] Yield: 84.3%

[0198] 1 HNMR (400MHz, CDCl 3 )δ: 5.32(2H,),7.30-7.56(7H,m),7.68-7.80(2H,m),7.82-7.90(1H,m),8.13(1H,s),8.18-8.21(1H,m ),8.24-8.33(1H,m),8.54-8.64(1H,m)

[0199] Process 3

[0200] Yield: 94.2%

[0201] 1 HNMR (400MHz, CDCl 3 )δ: 5.33(2H,s),7.34-7.57(5H,m),7.41(1H,dd,J=2.44,8.80Hz),7.68-7.77(2H,m),7.98(1H,d,J= 8.80Hz), 8.14(1H,d,J=2.44Hz), 8.54-8.64(1H,m), 8.21(11H,s), 9.36-9.44(1H,m), 10.33(1H,s)

[0202] Process 4

[0203] Yield: 98.8%

[0204] 1 HNMR (400MHz, CDCl 3 ...

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

A novel compound having an excellent NFºB inhibitory effect is provided and specifically disclosed is a compound represented by the following formula (1) or a salt thereof: wherein, R 1 represents a hydrogen atom, a lower alkyl group, a lower alkyloxy group, or a halogen atom; R 2 represents a hydroxyl group, or a lower alkyloky group; R 3 represents a hydrogen atom, a lower alkyl group, or a halogen atom; R 4 represents a hydrogen atom or a lower alkyloxy group; R 5 represents a hydrogen atom, a lower alkyloxy group, a halogen atom, a hydroxyl group, or a methylenedioxy group formed together with R 6 or an isopropylidenedioxy group formed together with R 6 ; R 6 represents a hydrogen atom, a lower alkyloxy group, or a methylenedioxy group formed together with R 5 or an isopropylidenedioxy group formed together with R 5 ; R 7 represents a hydrogen atom or a lower alkyl group; and R 8 represents a hydrogen atom, a hydroxyl group, an amino group, or a lower alkylcarbonyloxy group (excluding the case where R 1 , R 3 , R 4 and R 7 are hydrogen atoms, R 2 and R 8 are hydroxyl groups, and R 5 and R 6 are methoxy groups).

Description

[0001] This case is filed on October 23, 2009 , the application number is 200980141088.6 , the name of the invention is Phenanthrene indorisidine compound and NFκB inhibitor using it as an active ingredient divisional application of the patent application. technical field [0002] The present invention relates to Nuclear Factor-κB (nuclear factor-κB, hereinafter, sometimes also referred to as NFκB) inhibitors. More specifically, it relates to a novel phenanthrene indorisidine alkaloid compound or a salt thereof that inhibits NFκB, and a drug containing them. Background technique [0003] NFKB exists as a dimer formed by various combinations of NFKB family members p50, p65 / RelA, c-Rel, Rel-B and p52. Among them, the most well-known dimer is a heterodimer formed by a 50 kDa subunit (p50) and a 65 kDa subunit (p65). [0004] The heterodimer usually exists in an inactive state combined with inhibitor of NFκB (IκB) in the cytoplasm, but once the cells are stimulated by infla...

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 Applications(China)
IPC IPC(8): C07D471/04A61K31/437A61P35/00A61P29/00
CPCC07D471/04C07D491/147A61P1/00A61P3/04A61P3/10A61P9/08A61P9/10A61P11/06A61P17/00A61P17/06A61P19/02A61P25/28A61P29/00A61P31/04A61P31/12A61P35/00A61P35/04A61P37/02A61P37/06A61P37/08A61P43/00
Inventor 池田隆史泽田诚吾八重樫隆松崎健桥本秀介山崎龙太
Owner YAKULT HONSHA KK
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

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

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap