Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Pleuromutilin derivative with pyrimidine side chain and application of pleuromutilin derivative

A technology of pleuromutilin and derivatives, applied in the direction of organic chemistry, antibacterial drugs, etc.

Active Publication Date: 2015-07-29
山东齐发药业有限公司
View PDF7 Cites 10 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the overuse of antibiotics has led to serious drug resistance in many 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
  • Pleuromutilin derivative with pyrimidine side chain and application of pleuromutilin derivative
  • Pleuromutilin derivative with pyrimidine side chain and application of pleuromutilin derivative
  • Pleuromutilin derivative with pyrimidine side chain and application of pleuromutilin derivative

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0020] Example 1: 14-O-[(4-Amino-6-hydroxy-pyrimidin-2-yl)thioacetyl]Multiline

[0021] Dissolve 1.65 g of 4-amino-6-hydroxy-2-mercaptopyrimidine monohydrate (10 mmol) in 20 mL of methanol, add 1.1 mL of 10 M NaOH (11 mmol) and stir for 30 min. Then 20 mL of dichloromethane (DCM) solution containing 5.33 g (10 mmol) 22-O-(4-tosyl)oxyacetylmtilin was added dropwise, and stirred at room temperature for 36-40 h after the addition was complete. After evaporating the solvent under reduced pressure, the crude product was dissolved in a mixed solution of 60mL ethyl acetate and 20mL water, and 50mL saturated NaHCO 3 Afterwards, a large amount of white precipitate was produced, and after filtration, it was separated by column chromatography (ethyl acetate:ethanol=20:1) to obtain the target compound.

[0022] Due to the structural tautomerism of the hydroxyl and ketone formulas, the 14-O-[(4-amino-6-hydroxy-pyrimidin-2-yl)thioacetyl]muroline tautomer is 14-O-[(4 -Amino-6-ketone-pyrimi...

Embodiment 2

[0028] Example 2: 14-O-[(4-Amino-6-methoxy-pyrimidin-2-yl)thioacetyl]Multiline

[0029] 2.51g of 14-O-[(4-amino-6-hydroxy-pyrimidin-2-yl) thioacetyl] monoclonal (5.0mmol) and 2.07g of K 2 CO 3 (15 mmol) was dissolved in 20 mL of dimethylformamide (DMF), then 0.71 g of iodomethane (5.0 mmol) was added in portions. Stir the reaction at 80-85°C for 4h, cool the reaction system, filter the insoluble impurities, and evaporate the solvent to dryness under reduced pressure. The resulting mixture was separated by column chromatography (petroleum ether: ethyl acetate = 1:15) to obtain 1.7 g (28%) of 14-O-[(4-amino-6methoxy-pyrimidin-2-yl ) thioacetyl]Miltiline and 3.6 g (61%) of 14-O-[(1-methyl-4-amino-6-keto-pyrimidin-2-yl)thioacetyl]Miltiline.

[0030] 14-O-[(4-Amino-6-methoxy-pyrimidin-2-yl)thioacetyl]Multiline, the structural formula is as follows:

[0031]

[0032]IR(KBr)3374,2928,1732,1626,1585,1548,1390,1307,1273,1212,1152,1117,1048,1017,982,917cm -1 ; 1 H NMR (400MHz, ...

Embodiment 3

[0033] Example 3: 14-O-[(1-Methyl-4-amino-6-keto-pyrimidin-2-yl)thioacetyl]Multiline

[0034] The preparation method of 14-O-[(1-methyl-4-amino-6-keto-pyrimidin-2-yl)mercaptoyl]Multiline is the same as in Example 2, and the structural formula is as follows:

[0035]

[0036] IR (KBr) 3422, 2929, 1730, 1630, 1509, 1457, 1414, 1282, 1154, 1117, 1094, 807; 1 H NMR (400MHz, DMSO) δ6.28(s, 2H), 6.10(dd, J=17.8, 11.2Hz, 1H), 5.52(d, J=8.1Hz, 1H), 5.05(dd, J=27.5, 14.5Hz, 2H), 4.92(s, 1H), 4.52(d, J=5.9Hz, 1H), 4.34-3.68(m, 3H), 3.31(d, J=18.8Hz, 4H), 2.40(s, 1H),2.27-1.88(m,5H),1.83-1.58(m,2H),1.58-1.24(m,8H),1.18(t,J=7.1Hz,2H),1.05(s,4H),0.82 (d,J=6.8Hz,3H),0.61(d,J=6.8Hz,3H); 13 C NMR(100MHz,DMSO)δ217.55,170.79,166.83,161.88,161.51,160.51,141.22,115.85,81.23,73.13,70.83,60.22,57.65,45.43,44.63,43.90,42.04,40.56,40.30,40.14,39.83,39.62 ,39.41,36.82,34.56,30.57,29.38,29.07,27.09,24.93,21.23,16.61,14.89,14.56,11.98; LRMS(ES)calcd[M+H] + for C 27 h 39 N 3 o 5 S 518.2683, f...

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 a pleuromutilin derivative with a pyrimidine side chain. The structural formula of the derivative is shown in the specification, wherein R1 is C1-C4 alkoxy groups or hydroxyl groups; R2 is an amino group or an amide group; R3 is hydrogen or C1-C4 alkyl groups. The compound can be applied to preparation of antibacterial drugs, particularly to preparation of MRSA (methicillin-resistant staphylococcus aureus), MRSE (methicillin-resistant staphycoccus epidermidis) and / or antagonistic bacillus subtilis drugs, and the antibacterial effect is superior to that of tiamulin.

Description

technical field [0001] The invention belongs to the field of chemical medicines, and in particular relates to a pleuromutilin derivative with a pyrimidine side chain and an application thereof. Background technique [0002] The discovery of antibiotics has played an important role in human history. However, the overuse of antibiotics has led to serious drug resistance in many bacteria. Drug-resistant bacteria, especially Staphylococcus pneumoniae, Streptococcus pneumoniae, Mycobacterium tuberculosis, etc., cause more than two million deaths every year, seriously threatening human health. Therefore, it is particularly important to develop new anti-drug-resistant fungal drugs. [0003] Pleuromutilin (see formula i for chemical structure) is a diterpene compound with antibacterial activity isolated from the higher fungi Pleurotus multilus (Fr.) Sacc. and Pleurotus Passecke‐rianus Pilat for the first time in the 1950s. The compound consists of a 5‐6‐8 three-membered ring skel...

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
IPC IPC(8): C07D239/56C07D401/12A61P31/04
CPCC07D239/56C07D401/12
Inventor 尚若锋衣云鹏梁剑平郝宝成刘宇郭志廷
Owner 山东齐发药业有限公司
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com