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

Azithromycin derivative as well as intermediate, preparation method and application thereof

A technology of azithromycin and derivatives, applied in the field of new compounds, can solve problems such as poor activity of macrolide-resistant bacteria

Inactive Publication Date: 2012-05-23
SHANGHAI INST OF PHARMA IND CO LTD
View PDF3 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] But these antibiotics are still poorly active against macrolide-resistant bacteria

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
  • Azithromycin derivative as well as intermediate, preparation method and application thereof
  • Azithromycin derivative as well as intermediate, preparation method and application thereof
  • Azithromycin derivative as well as intermediate, preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0146] Example 1 4"-(2-acetyl) carbazate azithromycin (compound 1)

[0147] 2'-O-acetyl-4"-carbazate azithromycin (E 1 ) (0.353mmol), acetic acid (1.767mmol) and DCC (1.767mmol) were synthesized according to the general method, then filtered to remove insoluble matter, stirred with water, adjusted to pH=3.0-3.5, separated the water phase, and the water phase was oxidized with 3.0N hydroxide The sodium solution was used to adjust the pH to 9.3-9.7, extracted with dichloromethane, the organic phases were combined, washed with water, dried over anhydrous sodium sulfate, filtered, and drained to obtain a crude product. It was dissolved in methanol, refluxed for 18h, the solvent was evaporated to dryness under reduced pressure, dry column chromatography, the volume ratio of ethyl acetate:petroleum ether:diethylamine was 5:10:0.5 as the eluent, and the product was obtained 0.101g , yield 33.7%.

[0148] MS (ESI + , m / e): 849 [M+H] +

[0149] 1 HNMR (CDCl 3 , 400M) δ (ppm):

...

Embodiment 2

[0153] Example 2 4"-(2-hexadecanoyl) carbazate azithromycin (compound 2)

[0154] 2'-O-acetyl-4"-carbazate azithromycin (E 1 ) (0.353mmol), hexadecanoic acid (1.767mmol) and DCC (1.767mmol) were synthesized according to the general method, then filtered to remove the insoluble matter, stirred with water, adjusted to pH=3.0-3.5, separated the water phase, and used 3.0 Adjust the pH to 9.3-9.7 with N sodium hydroxide solution, extract with dichloromethane, combine the organic phases, wash with water, dry over anhydrous sodium sulfate, filter, and drain to obtain a crude product. It was dissolved in methanol, refluxed for 18h, evaporated to dryness under reduced pressure, dry column chromatography, the volume ratio of ethyl acetate:petroleum ether:diethylamine was 5:13:0.6 as the eluent, and the product was 0.187g , yield 50.7%.

[0155] MS (ESI + , m / e): 1045 [M+H] +

[0156] 1 HNMR (CDCl 3 , 400M) δ (ppm):

[0157] 5.21(d, 1H, 11-CH-), 5.11-5.08(d, 1H, -OH), 4.96-4.95(d...

Embodiment 3

[0160] Example 3 4"-[2-(2-methylpropionyl)]carbazate azithromycin (compound 3)

[0161] 2'-O-acetyl-4"-carbazate azithromycin (E 1 ) (0.353mmol), isobutyric acid (1.767mmol) and DCC (1.767mmol) were synthesized according to the general method, then filtered to remove insoluble matter, stirred with water, adjusted to pH = 3.0 ~ 3.5, separated the water phase, and used 3.0N Adjust the pH to 9.3-9.7 with sodium hydroxide solution, extract with dichloromethane, combine the organic phases, wash with water, dry over anhydrous sodium sulfate, filter, and drain to obtain a crude product. It was dissolved in methanol, refluxed for 24h, evaporated to dryness under reduced pressure, dry column chromatography, ethyl acetate:petroleum ether:diethylamine volume ratio was 5:5:0.3 as eluent, and 0.163g of product was obtained , yield 52.6%.

[0162] MS (ESI + , m / e): 877[M+H] +

[0163] 1 HNMR (CDCl 3 , 400M) δ (ppm):

[0164] 9.45-7.40 (d, 2H, 4”-OCONHNH-), 5.15 (d, 1H, 11-CH-), 4.50...

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 an azithromycin derivative as well as an intermediate, a preparation method and application thereof. The azithromycin derivative of the invention has stronger antibiosis activity, particularly on gram positive bacteria. The azithromycin derivative is shown in formula I.

Description

technical field [0001] The present invention relates to a novel compound, its intermediate, its preparation method and application, in particular to an azithromycin derivative, its intermediate, its preparation method and application. Background technique [0002] Erythromycin is still widely used because of its good antibacterial activity and safety. In the 1980s, the second-generation macrolide antibiotics such as clarithromycin, roxithromycin, dirithromycin, and azithromycin came out successively. Compared with erythromycin, this type of antibiotic has enhanced acid resistance, expanded antibacterial spectrum, and improved pharmacokinetic properties. It has strong antibacterial activity against gram-positive bacteria, some gram-negative bacteria, mycoplasma, etc. A medicine for treating infections caused by bacteria. Some of them have been used clinically as excellent antibiotics. For example, azithromycin (see USP 4,474,768 and USP 4,517,359 J.Chem.Research (S) (1988)...

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): C07H17/00C07H1/00A61K31/7052A61P31/04
CPCY02P20/55
Inventor 沈舜义葛涵刘毓彬
Owner SHANGHAI INST OF PHARMA IND CO LTD