Chiral fluoroquinolone C-3 fused heterocycle alpha, beta-unsaturated ketone derivative as well as preparation method and application thereof

A fluoroquinolone, C-3 technology, applied in the field of chiral fluoroquinolone C-3 fused heterocycle α, to achieve the effect of increasing anti-tumor activity and reducing toxic and side effects

Inactive Publication Date: 2015-04-08
HENAN UNIVERSITY
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, among the many (fused) heterocycles, which are the suitable isosteres of the C-3 carboxyl group and how to further optimize the isosteres, little is known at present

Method used

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  • Chiral fluoroquinolone C-3 fused heterocycle alpha, beta-unsaturated ketone derivative as well as preparation method and application thereof
  • Chiral fluoroquinolone C-3 fused heterocycle alpha, beta-unsaturated ketone derivative as well as preparation method and application thereof
  • Chiral fluoroquinolone C-3 fused heterocycle alpha, beta-unsaturated ketone derivative as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0055] The chiral fluoroquinolone C-3 condensed heterocyclic α, β-unsaturated ketone derivative in this example is (S)-6-fluoro-7-(4-methyl-piperazin-1-yl)-1, 8-(3,1-Oxopropyl)-3-[5-Benzylidene-thiazolo[3,2-b][1,2,4]triazol-6(5H)-one-2- Base]-quinolin-4(1H)-one, its chemical structural formula is:

[0056]

[0057] That is, Ar in formula (I) is phenyl.

[0058] The preparation method of the chiral fluoroquinolone C-3 condensed heterocyclic α, β-unsaturated ketone derivative of the present embodiment is as follows: take 1.0 g (2.4 mmol) of (S)-6-fluoro-7-(4-methyl Base-piperazin-1-yl)-1,8-(3,1-oxopropyl)-3-(5-mercapto-1,2,4-4H(1H)triazol-3-yl)-quinone Lin-4 (1H)-one (V) and 0.31g (2.9mmol) of benzaldehyde, 0.27g (2.9mmol) of chloroacetic acid, add glacial acetic acid (7ml) containing 0.24g (2.9mmol) of anhydrous sodium acetate In a mixed solvent with acetic anhydride (3ml), reflux reaction for 12h; evaporate the solvent under reduced pressure, add absolute ethanol (10ml) ...

Embodiment 2

[0060] The chiral fluoroquinolone C-3 condensed heterocyclic α, β-unsaturated ketone derivative in this example is (S)-6-fluoro-7-(4-methyl-piperazin-1-yl)-1, 8-(3,1-Oxopropyl)-3-[5-p-methoxybenzyl-thiazolo[3,2-b][1,2,4]triazol-6(5H)-one -2-yl]-quinolin-4 (1H)-one, its chemical structural formula is:

[0061]

[0062] That is, Ar in formula (I) is p-methoxyphenyl.

[0063] The preparation method of the chiral fluoroquinolone C-3 condensed heterocyclic α, β-unsaturated ketone derivative of the present embodiment is as follows: take 1.0 g (2.4 mmol) of (S)-6-fluoro-7-(4-methyl Base-piperazin-1-yl)-1,8-(3,1-oxopropyl)-3-(5-mercapto-1,2,4-4H(1H)triazol-3-yl)-quinone Lin-4(1H)-ketone (V) and 0.40g (2.9mmol) of p-methoxybenzaldehyde, 0.21g (2.5mmol) of chloroacetic acid, add ice containing 0.24g (2.9mmol) of anhydrous sodium acetate In a mixed solvent of acetic acid (7ml) and acetic anhydride (3ml), reflux for 12 hours; evaporate the solvent under reduced pressure, add absolut...

Embodiment 3

[0065] The chiral fluoroquinolone C-3 condensed heterocyclic α, β-unsaturated ketone derivative in this example is (S)-6-fluoro-7-(4-methyl-piperazin-1-yl)-1, 8-(3,1-Oxopropyl)-3-[5-o-methoxybenzyl-thiazolo[3,2-b][1,2,4]triazol-6(5H)-one -2-yl]-quinolin-4 (1H)-one, its chemical structural formula is:

[0066]

[0067] That is, Ar in formula (I) is o-methoxyphenyl.

[0068] The preparation method of the chiral fluoroquinolone C-3 condensed heterocyclic α, β-unsaturated ketone derivative of the present embodiment is as follows: take 1.0 g (2.4 mmol) of (S)-6-fluoro-7-(4-methyl Base-piperazin-1-yl)-1,8-(3,1-oxopropyl)-3-(5-mercapto-1,2,4-4H(1H)triazol-3-yl)-quinone Lin-4(1H)-one (V) and 0.40g (2.9mmol) of o-methoxybenzaldehyde, 0.23g (2.5mmol) of chloroacetic acid, add ice containing 0.24g (2.9mmol) of anhydrous sodium acetate In a mixed solvent of acetic acid (7ml) and acetic anhydride (3ml), reflux for 12 hours; evaporate the solvent under reduced pressure, add absolute e...

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Abstract

The invention discloses a chiral fluoroquinolone C-3 fused heterocycle alpha, beta-unsaturated ketone derivative as well as a preparation method and application thereof. The chiral fluoroquinolone C-3 fused heterocycle alpha, beta-unsaturated ketone derivative is a compound having the general structural formula (I), wherein Ar represents phenyl, substituted phenyl or pyridyl. According to the chiral fluoroquinolone C-3 fused heterocycle alpha, beta-unsaturated ketone derivative disclosed by the invention, three medicinal groups with different structural characteristics, including fluoroquinolone, a fused heterocycle of thiadiazole and s-triazole, and alpha, beta-unsaturated ketone are spliced to build a chiral fluoroquinolone-fused heterocycle-unsaturated ketone derivative and realize structural compensation and overlapping of the three medicinal groups, including the fluoroquinolone, thiazole [3,2-b][1,2,4] triazole and the alpha, beta-unsaturated ketone, so that the antitumor activity of a new compound is improved, toxic and side effects on normal cells are reduced, and the chiral fluoroquinolone C-3 fused heterocycle alpha, beta-unsaturated ketone derivative can be used as an antitumor active substance for developing an antitumor drug with a totally new structure.

Description

technical field [0001] The invention belongs to the technical field of antineoplastic drugs, and specifically relates to a chiral fluoroquinolone C-3 fused heterocyclic α, β-unsaturated ketone derivative, and also relates to a chiral fluoroquinolone C-3 fused heterocyclic α, Preparation method and application of β-unsaturated ketone derivatives. Background technique [0002] The discovery of new structural drugs is a high-risk, high-investment complex intellectual innovation activity, and the construction of chemical structures is the key link. Among them, the combination of pharmacophore and skeleton transition based on existing drugs is the most economical and reliable strategy . Based on the structure of 1-substituted-6-fluoro-quinoline (naphthyridine)-4-one-3-carboxylic acid, which is the basic pharmacophore skeleton of antibacterial quinolones, many excellent new antibacterial drugs can be produced by modifying the structure of other parts. At the same time, a new stu...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D519/00A61K31/5383A61P35/00
CPCC07D519/00
Inventor 胡国强李涛高留州谢玉锁冯焱飞闫强吴书敏倪礼礼
Owner HENAN UNIVERSITY
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