Semi-synthetic aminoglycoside antibiotic, preparation method and medicine composition thereof

An aminoglycoside and semi-synthetic technology, which is applied in the preparation of sugar derivatives, sugar derivatives, sugar derivatives, etc., can solve the problems of high production costs, and achieve the effects of high application value, high yield and pure products

Inactive Publication Date: 2012-01-18
CHANGZHOU FANGYUAN PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] The technical problem to be solved by this invention is that due to long-term use, most Mycobacterium tuberculosis has produced drug resistance to existing antibacterial drugs and the ear and nephrotoxicity of the existing anti-tuberculosis drugs belonging to antibiotics are relatively large, and the drug-resistant bacteria are provided. 1-N-acetyl minomycin or its salt with good antibacterial effect and reduced ototoxicity and renal toxicity. In addition, considering the characteristics that the production cost of this type of drug should not be too high, a high-efficiency and high-yield route is designed. In addition, it provides preparations containing the above active ingredients

Method used

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  • Semi-synthetic aminoglycoside antibiotic, preparation method and medicine composition thereof
  • Semi-synthetic aminoglycoside antibiotic, preparation method and medicine composition thereof
  • Semi-synthetic aminoglycoside antibiotic, preparation method and medicine composition thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0038] (Embodiment 1, 1-N-acetyl minonomycin and preparation method thereof)

[0039] The semi-synthetic aminoglycoside antibiotic of the present invention is 1-N-acetyl agnonomycin, and molecular formula is C 22 h 44 N 5 o 8 , the molecular weight is 506, and its conformational formula is as follows:

[0040]

[0041] 1-N-Acetyl Daunomycin is produced by semi-synthesis with Daunomycin base (Base) as the mother nucleus.

[0042] The reaction equation for the semi-synthetic preparation of 1-N-acetyldaunomycin with the agnonomycin base as the mother nucleus is as follows:

[0043]

[0044]

[0045] Note: E-MCR refers to 1-N-acetyl minonomycin, and the code name in the efficacy test example is: FY-2.

[0046] The starting material used in the preparation process is micronomycin sulfate, and the CAS number is 66803-19-8. The conformational formula of micronomycin sulfate is as follows:

[0047]

[0048] Described micronomycin sulfate meets the quality standard sti...

Embodiment 2

[0085] (embodiment 2, vitriol 1-N-acetyl agnonomycin and preparation method thereof)

[0086] 1-N-acetyl minonomycin sulfate is a 1-N-acetyl minonomycin molecule with 2.5 H 2 SO 4 Molecules combined, the molecular formula is C 22 h 44 N 5 o 8 ·5 / 2H 2 SO 4 , the molecular weight is 750, and its conformational formula is as follows:

[0087]

[0088] The preparation method of vitriol 1-N-acetyl minomycin is as follows:

[0089] Add the sulfuric acid of 3mol / L in the 50mL of the 1-N-acetyl group phenomycin concentrate obtained in embodiment 1, adjust concentrated solution pH to be 6.0; Add gac 5g to remove heat source again in above-mentioned mixed solution, filter and remove gac to obtain sulfuric acid Concentrate of 1-N-acetyl-minoromycin; then freeze-dry or spray-dry the above-mentioned concentrate to obtain 1-N-acetyl-minoromycin sulfate.

[0090] The prepared 1-N-acetyl minomycin sulfate is a loose solid of white or off-white powder, odorless and hygroscopic; It...

Embodiment 3

[0091] (Embodiment 3, 1-N-acetyl diaunomycin hydrochloride and preparation method thereof)

[0092] The molecular formula of 1-N-acetyl minonomycin hydrochloride is C 22 h 44 N 5 o 8 2HCl, the molecular weight is 578, its conformational formula is as follows:

[0093]

[0094] The rest of the preparation method of 1-N-acetyl minonomycin hydrochloride is the same as Example 2, except that:

[0095] The acid added to 50 mL of the concentrated solution of 1-N-acetyl diaunomycin obtained in Example 1 was 6N hydrochloric acid, and the pH of the concentrated solution was adjusted to be 6.0.

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Abstract

The invention discloses a semi-synthetic aminoglycoside antibiotic of 1-N-acetyl micronomicin, and pharmaceutically acceptable salt and a preparation method thereof. The preparation method of 1-N-acetyl micronomicin comprises the following steps: the formylation protection is carried out on C2'-NH2 and C3-NH2 of micronomicin basic groups, the 3,-2-two-N-formoxyl micronomicin, the acetylation reaction is then carried out to obtain 1-N-acetyl-3,-2-two-N-formoxyl micronomicin, the obtained products are subject to hydrolysis reaction in alkali solution, and the 1-N-acetyl micronomicin is obtained through formylation protection for removing 2'-NH2 and 3-NH2. The 1-N-acetyl micronomicin has the advantages that in-vitro antitubercular bacteria and antibiotic activity experiments prove that the 1-N-acetyl micronomicin has higher antibiotic activity to mycobacterium tuberculosis gram-positive bacteria and negative bacteria, in addition, the toxicity of medicine on ears and kidneys is greatly reduced, and higher clinical application value is realized.

Description

technical field [0001] The present invention relates to an aminoglycoside antibiotic, in particular to a new antibacterial compound 1-N-acetyl agnonomycin or its salt, its preparation method and a pharmaceutical composition containing the active ingredient. Background technique [0002] Since the American scholar Waxman discovered the first aminoglycoside antibiotic streptomycin (streptomycin) in 1944, after more than 60 years of development, this type of antibiotic has been widely used in the treatment of anti-infective diseases. Aminoglycoside antibiotics not only have a broad antibacterial spectrum, but also do not have fatal allergic reactions like penicillin. When aminoglycoside antibiotics are used in combination with β-lactam antibiotics, they have a better synergistic effect on severe patients. However, due to the side effects of certain ear and kidney aspects of these antibiotics, their widespread clinical use is limited. After the long-term efforts of scholars, ma...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07H15/234C07H1/00A61K31/7036A61P31/06
Inventor 范铭琦范瑾葛啸虎赵敏沈依群
Owner CHANGZHOU FANGYUAN PHARMA
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