Macrolide derivatives and application thereof

A technology of macrolides and derivatives, which is applied in the field of macrolides derivatives, can solve the problems of drug development and use limited by antibiotic activity, achieve enhanced gastrointestinal motility, low antibiotic activity, and promote digestive tract dynamic effect

Active Publication Date: 2016-11-23
TIANJIN INT JOINT ACADEMY OF BIOTECH & MEDICINE +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

When macrolide derivatives are used for other medical purposes, the side effects caused by their antibiotic activity greatly limit the development and use of drugs

Method used

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  • Macrolide derivatives and application thereof
  • Macrolide derivatives and application thereof
  • Macrolide derivatives and application thereof

Examples

Experimental program
Comparison scheme
Effect test

specific Embodiment approach

[0020] The present invention prepares compound macrolide derivatives through chemical reaction, by 1 H-NMR (proton nuclear magnetic resonance spectrum) and MS (mass spectrometry) carried out structure identification on macrolide derivatives. The antibacterial activity and the activity of promoting intestinal motility of the macrolide derivatives were detected through a series of experiments. The specific implementation is as follows:

[0021] In the following examples, used test materials and sources thereof include:

[0022] (1) mouse

[0023] Kunming mice (female): provided by the Experimental Animal Center of the Academy of Military Medical Sciences of the Chinese People's Liberation Army and Beijing Weitong Lihua Experimental Animal Technology Co., Ltd.

[0024] After the animals arrive, special personnel will receive the animals in the double-corridor barrier environment mouse breeding room, fill in the "Test Animal Reception Record Form" (BG-017-V00), observe the gene...

Embodiment 1

[0037] Synthesis and identification of embodiment 1 macrolide derivatives

[0038] Dissolve 28.58g (38.94mmol) of erythromycin A and 15.6g (224.4mmol) of hydroxylamine hydrochloride in 60.0ml of anhydrous methanol, then add 15.6ml (112.4mmol) of triethylamine, stir and heat under reflux for 24 hours, after the reaction is completed , cooling and suction filtration at 0°C, washing the filter cake with a small amount of methanol, suspending the resulting solid in 80ml of methanol, adding 20ml of ammonia water dropwise under stirring, filtering to remove insoluble substances, adding the methanol ammonia solution dropwise into 150ml of water, a large amount of white solids precipitated , filtered with suction, washed with water until neutral, and dried to obtain solid a (see figure 1 ), the productive rate is 80.6%, and the melting point is 163-166° C., and the mass spectrometry data is MS (M / Z): 749.75 (M+H + ).

[0039] Dissolve 0.1 g (0.134 mmol) of 9-oxime erythromycin A (a)...

Embodiment 2

[0045] Antibacterial activity test of embodiment 2 macrolide derivatives

[0046] experimental method:

[0047]1) Take 5 μL of Escherichia coli glycerol, inoculate into 5 mL of liquid LB medium, place in a shaker at 37°C, 220 rpm / min, and culture overnight;

[0048] 2) Pour the Escherichia coli cultured overnight into 250ml of LB medium, and culture at 37°C and 220rpm for 3 hours;

[0049] 3) After 3 hours, divide the bacterial solution in the Erlenmeyer flask into small test tubes, 5ml in each test tube, add 5μl of the same molar amount of derivatives to each test tube, incubate for 24 hours, test every 2-4 hours OD 600 Value, and calculate the bacteriostatic rate, bacteriostatic rate=(1-(OD of derivative 600 value) / (OD of DMSO blank group 600 value)) x 100%.

[0050] Antibacterial activity test results:

[0051] The bacteriostatic activity of macrolide derivatives is shown in Table 1 and Table 2, wherein Table 1 is the bacteriostatic rate under the concentration of 5.3...

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Abstract

The invention provides macrolide derivatives and application thereof. The general molecular formula of the macrolide derivatives is as shown in the description, wherein R1 is selected from hydrogen or a hydroxyl group or a halogen or a C1-C6 alkyl group or a C1-C4 alkoxy group or a C1-C6 alkenyl group or (CH2)m(C6-C10 aryl group) or (CH2)m(C5-C10 ceteroary) or a C2-C10 alkynyl group, R2 and R3 are each selected from hydrogen or a hydroxyl group or a halogen or a C1-C6 alkyl group or a C1-C6 alkenyl group or (CH2)m(C6-C10 aryl group) or (CH2)m(C5-C10 ceteroary) or a C2-C10 alkynyl group or a C1-C4 alkoxy group or a pyranose group, the pyranose group is unsubstituted or substituted with one or more of the following groups of hydrogen, halogen, a C1-C6 alkyl group, a C1-C4 alkoxy group, a C1-C4 alkyl acyl group and a C1-C4 alkyl acyloxy group, and each m is an independent integer ranging from 0 to 4. The compounds can be used for preparing drugs which have the function of promoting alimentary motility and are low in antibiotic activity and small in side effect.

Description

technical field [0001] The invention belongs to the field of medicinal chemistry, and in particular relates to macrolide derivatives and applications thereof. Background technique [0002] Digestive tract functional disease is one of the most common clinical diseases, and the vast majority of patients have gastrointestinal motility disorders, that is, gastrointestinal motility deficiency. Colonic motility in normal healthy individuals includes short-term contractions, long-term contractions, tonic contractions, and giant transitional contractions (GMCs). Under normal circumstances, the colon is mostly in a static or low-amplitude non-propelling phasic contraction state, while GMSs occur 1-2 times a day, causing group movements, which are related to defecation. The gastrocolic reflex is a main form of colon motility induced. The vast majority of patients with gastrointestinal dysfunction have no specific disease. Patients with functional constipation are mainly divided into...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/395A61K31/7052A61P1/14A61P1/10A61P1/00
CPCA61K9/12A61K9/20A61K31/395A61K31/7052
Inventor 杨诚孙涛周红刚刘慧娟孙波刘艳荣王静刘慧芳樊云静朱方娜张强肖婷孟晶仲威龙秦源张鹏张向明刘学强
Owner TIANJIN INT JOINT ACADEMY OF BIOTECH & MEDICINE
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