Unlock instant, AI-driven research and patent intelligence for your innovation.

Bis-fluoroquinolone oxadiazole urea derivatives containing N-methyl moxifloxacin as well as preparation method and application of derivatives

A technology of fluoroquinolone-based oxadiazuron and methylmoxifloxacin, which is applied in the field of new drug discovery and innovative drug synthesis

Inactive Publication Date: 2019-03-08
ZHENGZHOU UNIV OF IND TECH
View PDF2 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the question is what type of carboxyl isostere to choose, and what kind of connection to the fluoroquinolone skeleton will be conducive to the discovery of targeted small molecule leads, and further innovations to drive the discovery of targeted anti-tumor fluoroquinolone drugs still remain Current issues to be resolved

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
  • Bis-fluoroquinolone oxadiazole urea derivatives containing N-methyl moxifloxacin as well as preparation method and application of derivatives
  • Bis-fluoroquinolone oxadiazole urea derivatives containing N-methyl moxifloxacin as well as preparation method and application of derivatives
  • Bis-fluoroquinolone oxadiazole urea derivatives containing N-methyl moxifloxacin as well as preparation method and application of derivatives

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0048] The general method for the preparation of fluoroquinolone hydroxamic acid (1″~18″) is as follows: get the aforementioned fluoroquinolone carboxylic acid imidazolamide crude product (0.10 mol) and suspend it in 500mL pyridine, add hydroxylamine hydrochloride 7.0g~35.0g (0.1~0.5mol ), stirred and reacted in a water bath at 60-75°C for 8.0-24.0 hours, cooled to room temperature, collected the solid by filtration, washed the obtained solid with pyridine, dried in vacuum at 60-70°C, and dispersed in saturated sodium bicarbonate solution (500mL) again, 50 Stir in a water bath at ~65°C for 3 to 5 hours, collect the solid by filtration, wash with deionized water until the pH is 7.0, and dry to obtain the crude product. After recrystallization, analytically pure crystalline fluoroquinolone hydroxamic acid (1″-18″) was obtained.

[0049] General method for the preparation of target compound bis-fluoroquinolone-based oxadiazole derivatives containing N-methylmoxifloxacin: get 1.0 ...

Embodiment 1

[0053] 1-{2-[1-cyclopropyl-6-fluoro-8-methoxy-7-(1-methyl-octahydropyrrolo[3,4-b]pyridin-6-yl)-quinoline -4(1H)-keto-3-yl]-1,3,4-oxadiazol-5-yl}-3-[6-fluoro-7-(4-methylpiperazin-1-yl)- 8,1-(1,3-oxopropyl)-quinolin-4(1H)-one-3-yl]-urea (I-1), its chemical structural formula is:

[0054]

[0055] The preparation method of the bis-fluoroquinolone oxadiazuron of the present embodiment is: get ofloxacin hydroxamic acid (1 ") 1.0g (2.7 mmol) and suspend in 25mL acetonitrile, add carbonyldiimidazole (CDI) 0.79g (4.9mmol), stirring at room temperature until the material is dissolved. Then add 1.23g (2.7mmol) of N-methylmoxifloxacin C-3 oxadiazolamide II intermediate, and stir in a water bath at 55-60°C for 16 hours. Place overnight, filter The resulting solid was collected and washed with acetonitrile. The crude product was recrystallized from a mixed solvent of DMF-ethanol to obtain a light yellow crystal (I-1), with a yield of 56%, m.p.212-214°C. 1 H NMR (400MHz, DMSO-d 6 )δ: ...

Embodiment 2

[0057] (S)-1-{2-[1-cyclopropyl-6-fluoro-8-methoxy-7-(1-methyl-octahydropyrrolo[3,4-b]pyridin-6-yl )-quinoline-4(1H)-one-3-yl]-1,3,4-oxadiazol-5-yl}-3-[6-fluoro-7-(4-methylpiperazine-1 -yl)-8,1-(1,3-oxopropyl)-quinolin-4(1H)-one-3-yl]-urea (I-1), its chemical structural formula is:

[0058]

[0059] The preparation method of the bis-fluoroquinolone oxadiazuron of the present embodiment is: take levofloxacin hydroxamic acid (2″) 1.0g (2.7 mmol) and suspend in 25mL acetonitrile, add carbonyldiimidazole (CDI) 0.70g (4.3mmol ), stirred at room temperature until the material was dissolved. Then 1.23g (2.7mmol) of N-methylmoxifloxacin C-3 oxadiazole amine II intermediate was added, stirred in a water bath at 55-60°C for 10 hours. Placed overnight, and the resulting The solid was washed with acetonitrile. The crude product was recrystallized from ethanol to obtain a light yellow crystal (I-2), with a yield of 46%, m.p.206-208°C. 1 H NMR (400MHz, DMSO-d 6 )δ:11.64(brs,1H,NH), 9.5...

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 discloses bis-fluoroquinolone oxadiazole urea derivatives containing N-methyl moxifloxacin as well as a preparation method and an application of the derivatives. The general chemical structural formula of the derivatives is represented as the formula I shown in the description; in in the general formula, R is -CH2-CH3, cyclopropyl or -CH2-CH2F, L is -Cl, -F, 1-piperazinyl, substituted piperazine-1-yl or nitrogenous heterocyclic ring, X is -CH, -N, -CF or -COCH3, or R and X jointly constitute an oxazine ring or a thiazine ring. According to the bis-fluoroquinolone oxadiazole ureaderivatives, organic splicing of a bis-fluoroquinolone skeleton, an oxadiazole heterocyclic ring and functional ureas is realized, hopping and stacking of different pharmacophores are realized, antitumor activity and selectivity of fluoroquinolone are improved, toxic and side effects on normal cells are reduced, and the derivatives can be used as antitumor active substances to develop antitumor drugs with brand-new structure.

Description

technical field [0001] The invention belongs to the technical field of new drug discovery and innovative drug synthesis, and specifically relates to a bis-fluoroquinolone-based oxadiazole derivative containing N-methylmoxifloxacin, and also relates to a preparation method of the derivative, and Its application in antineoplastic drugs. Background technique [0002] The research and development of new drugs originates from the discovery of lead substances, and the structural optimization of lead substances is the key link to promote their development into finished drugs. A rational drug design strategy based on structure or mechanism, using the dominant skeleton or pharmacophore fragments of existing drugs to create new small molecule leads with therapeutic and functional regulation for major diseases such as malignant tumors is the most economical and effective strategy for new drug development. Based on this, on the one hand, it is considered that fluoroquinolones (FQs) are...

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): C07D519/00A61P35/00A61P35/02
CPCA61P35/00A61P35/02C07D519/00
Inventor 岑世宏耿胜男杨莉胡国强
Owner ZHENGZHOU UNIV OF IND TECH