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Macrolide derivative and application thereof

A technology of macrolides and derivatives, applied in the field of macrolides derivatives, can solve the problem of lack of similar compounds

Inactive Publication Date: 2017-03-08
NANKAI UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0005] The present invention aims at the technical defects of the prior art, and provides a macrolide derivative and its use, so as to solve the technical problem of lacking a similar compound in the prior art

Method used

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  • Macrolide derivative and application thereof
  • Macrolide derivative and application thereof
  • Macrolide derivative and application thereof

Examples

Experimental program
Comparison scheme
Effect test

specific Embodiment approach

[0027] 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:

[0028] In the following examples, used test materials and sources thereof include:

[0029] (1) mouse

[0030] 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.

[0031] 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

[0044] Synthesis and identification of embodiment 1 macrolide derivatives

[0045] 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 + ).

[0046] Dissolve 0.1 g (0.134 mmol) of 9-oxime erythromycin A (a)...

Embodiment 2

[0052] Antibacterial activity test of embodiment 2 macrolide derivatives

[0053] experimental method:

[0054]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;

[0055] 2) Pour the Escherichia coli cultured overnight into 250ml of LB medium, and culture at 37°C and 220rpm for 3 hours;

[0056] 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%.

[0057] Antibacterial activity test results:

[0058] 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 a macrolide derivative of a novel structure. Experiments show that the macrolide derivative has a good promoting effect on alimentary motility and is capable of enhancing intestine peristalsis, increasing defecation quantity and accelerating passing of intestinal content; on such basis, it is further discovered that the macrolide derivative is low in antibiotic activity and small in side effect and can be taken as a gastrointestinal motility promoting drug. Particularly, a compound III-3 screened with the optimal efficacy is subjected to further efficacy evaluation as well as acute toxicity and cardiotoxicity evaluation by domestic rabbits, beagles and marmosets. Experiments show that the compound III-3 is safe and capable of effectively promoting gastrointestinal motility, thereby being excellent in druggability.

Description

technical field [0001] The present invention relates to the technical field of medicinal chemistry, and further relates to novel compounds and their uses, in particular to macrolide derivatives and their uses. Background technique [0002] Digestive tract functional disease is one of the most common clinical diseases, and the vast majority of patients have digestive tract 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 inducing colonic movement. The vast majority of patients with gastrointestinal dysfunction have no specific disease. Patients...

Claims

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Application Information

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IPC IPC(8): C07D267/00C07H17/00A61K31/7048A61K31/395A61P1/14A61P1/10A61P1/00
CPCC07D267/00C07H17/00
Inventor 杨诚孙涛周红刚杨光
Owner NANKAI UNIV
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