47 results about "Pleuromutilin" patented technology

The invention discloses a preparation method of tiamulin and tiamulin fumarate based on Bunte salt, which comprises the following steps: mixing the Bunte salt and pleuromutilin p-toluenesulfonate, reacting at 45-65 DEG C for 3-5 hours to synthesize tiamulin, preparing the Bunte salt through a reaction formula 1, and preparing the pleuromutilin p-toluenesulfonate through a reaction formula 2, the molar ratio of the 2-diethylaminoethanol to the sodium thiosulfate to the chlorination reagent in the reaction formula 1 is 1: (1-1.3): (1-1.5), and the molar ratio of the pleuromutilin to the paratoluensulfonyl chloride to the pyridine in the reaction formula 2 is 1: (1-1.2): (1-1.2); the prepared tiamulin and fumaric acid are used as raw materials for a salt forming reaction, the reaction temperature ranges from 55 DEG C to 65 DEG C, the reaction time ranges from 40 min to 80 min, and after the reaction is finished, the tiamulin fumarate is prepared through cooling, crystallization, centrifugation and drying; the tiamulin fumarate disclosed by the invention is high in content, low in total amount of impurities, few in variety and stable in quality under high-temperature and high-humidity conditions, and the preparation method is simple and easy to operate and good in product quality.

The invention relates to the technical field of chemical synthesis of medicines, in particular to a pleuromutilin derivative, a preparation method thereof and an antibacterial active composition. The structural formula of the pleuromutilin derivative is a compound with a structure as shown in a formula I, or pharmaceutically and / or veterinarily acceptable salt, a solvent compound, an optical isomer and a polymorphic compound of the pleuromutilin derivative, wherein R is selected from any one of a group consisting of R and R. According to the scheme provided by the invention, the compound has good antibacterial activity and is suitable for being used as a novel antibacterial drug for preventing and treating human or animal bacterial infectious diseases.

The present invention provides e / zz'-pleuromutilin triazole derivatives and e / zz'-tiamulin triazole derivatives with antibacterial activity.

The utility model relates to the technical field of industrial production of pleuromutilin, and specifically discloses a pleuromutilin extraction system to solve the problems of low yield, insufficient purity and low efficiency of clarity treatment in the existing pleuromutilin extraction mode, which comprises a three-stage countercurrent leaching system, a double-effect evaporation system, a methanol evaporation kettle, a layered tank and a vacuum evaporation crystallization system connected in sequence from the head to the tail. The three-stage countercurrent leaching system comprises three countercurrent leaching tanks and dryers connected in series from the head to the tail, and the discharge end of the first countercurrent leaching tank and the discharge end of the second countercurrent leaching tank are both provided with a slag excavator, and the discharge end of the third countercurrent leaching tank is provided with a slag extruder. The extraction system is used for extracting and processing pleuromutilin, and the pleuromutilin has high yield, high degree of automation and high purity.

The invention relates to the technical field of chemical synthesis of medicines, in particular to a pleuromutilin derivative, a preparation method thereof and an antibacterial active composition. The invention relates to a pleuromutilin derivative with a structure as shown in a formula I, or pharmaceutically and / or veterinary acceptable salt, a solvent compound, an optical isomer and a polymorphic compound of the pleuromutilin derivative. Formula I; wherein R1 is selected from one of a hydrogen atom and methyl; r2 is selected from one of a hydrogen atom and a methoxy group; and R3 is selected from one of cyclopropyl and p-fluorophenyl. According to the present invention, the quinolone drug is spliced to the pleuromutilin side chain to produce the new pleuromutilin derivative, and the obtained new compound can enhance the antibacterial activity, has significant antibacterial activity on Gram-positive bacteria and Gram-negative bacteria, and further has significant inhibition effect on MRSA and other drug-resistant bacteria so as to effectively broaden the antibacterial spectrum.

The invention relates to a pleuromutilin derivative as well as a preparation method and application thereof. The structure of the pleuromutilin derivative is a compound as shown in a formula (I), and a stereoisomer, a tautomer or pharmaceutically acceptable salt thereof. The invention also provides a preparation method of the pleuromutilin derivative. The invention also provides an application of the pleuromutilin derivative in preparation of antibiotics and / or anti-mycoplasma drugs. The invention provides a novel drug which shows good antibacterial activity in vivo and in vitro, so that the problem of drug resistance of existing antibiotics is solved. # imgabs0 #

The invention provides a pleuromutilin producing strain, a fermentation product and application of the pleuromutilin producing strain, and belongs to the technical field of microorganisms. The pleuromutilin producing strain BEP200910 is a strain which is preserved in the China General Microbiological Culture Collection Center (CGMCC), and the preservation number of the strain is CGMCC No.42030. The pleuromutilin producing strain BEP200910 can be used for producing pleuromutilin. The pleuromutilin producing strain disclosed by the invention can be used for producing pleuromutilin through fermentation, the fermentation yield is obviously higher than that of a known pleuromutilin producing strain ATCC 34646, and a new way is provided for further improving the yield of pleuromutilin. Meanwhile, a fermentation product of the strain has an obvious bacteriostatic effect, can effectively inhibit growth of staphylococcus aureus and bacillus subtilis, and has a good application prospect in preparation of antibacterial drugs.

The present application relates to a pleuromutilin derivative, a preparation method and application thereof. The pleuromutilin derivative is a compound as shown in formula (I) and stereoisomers, tautomers or pharmaceutically acceptable salts thereof. The present application also provides a preparation method of the pleuromutilin derivative. The present application also provides application of the pleuromutilin derivative in preparation of antibacterial and / or anti-mycoplasma drugs. The present application provides a new drug which exhibits good antibacterial activity in vivo and in vitro, thereby solving the problem of drug resistance of existing antibiotics.

The present invention discloses a pleuromutilin derivative containing a 2-thio-4-thiazolidinone side chain, and its preparation method and application. The preparation method is as follows: first, pleuromutilin and p-toluenesulfonyl chloride are added to methyl tert-butyl ether, sodium hydroxide solution is added dropwise with stirring, and the reaction is refluxed to obtain intermediate 1; then, 2-thio-4-thiazolidinone is added to acetonitrile, anhydrous potassium carbonate is added and stirred at room temperature for 20 minutes, and then intermediate 1 is added, and the reaction is stirred at room temperature for a certain time to obtain intermediate 2; finally, intermediate 2 and an acyl chloride with different group donors are added to dichloromethane, and under the catalysis of triethylamine, stirred at room temperature for a certain time to obtain a pleuromutilin derivative containing a 2-thio-4-thiazolidinone side chain. The present invention synthesizes a pleuromutilin derivative containing a 2-thio-4-thiazolidinone side chain with good antibacterial activity through a simple preparation process, with high yield, good antibacterial activity against drug-resistant bacteria, and good application prospects.

The invention discloses a preparation method and application of pleuromutilin and derivatives thereof. The preparation of C7-site substituted, C8-site axial substituted and C8-site exocyclic double bond substituted derivatives of pleuromutilin is realized. The pleuromutilin derivative shows activity which is obviously superior to that of a parent compound pleuromutilin in the aspect of inhibiting proliferation of human cancer cells (such as breast cancer MDA-MB-231 cells and liver cancer HepG2 cells) with high expression of TrxR. Wherein the C8-position axially substituted derivative has particularly outstanding advantages in the aspect of inhibiting TrxR enzyme activity, and compared with a parent compound pleuromutilin and a positive control drug Jinnofen, the TrxR inhibiting efficacy of the C8-position axially substituted derivative is improved to 9 times and 16.7 times respectively.

The present application relates to the technical field of antibacterial drugs, and specifically discloses a pleuromutilin derivative and a use thereof, wherein the pleuromutilin derivative has a structure of being connected to a side chain of C14 of pleuromutilin by a mercaptoethylamine, piperazine or oxygen atom from a dihydroflavone or oxime ether derivative thereof. The present application introduces dihydroflavone (naringenin and hesperetin) and oxime ether derivatives thereof having antibacterial effects into the side chain of C14 of pleuromutilin by taking pleuromutilin as a raw material. The dihydroflavone and oxime ether derivatives thereof have great potential as an advantageous structural unit due to their unique C6-C3-C6 basic skeleton (C2 and C3 are single bonds) and extensive antibacterial activity. The dihydroflavone and oxime ether derivatives thereof are combined with pleuromutilin to synthesize a plurality of dihydroflavone pleuromutilin derivatives having excellent antibacterial activity. The present application provides a new choice for designing a new generation of pleuromutilin derivatives by a hybrid strategy, improving drug properties while improving activity, and providing an anti-infective drug.

The application discloses a truncated pleuromutilin oxazolopyridinium salt derivative having allosteric regulation on a bacterial peptide transferase center, a preparation method and application thereof, and belongs to the field of medicinal chemistry. 14 The truncated pleuromutilin oxazolopyridinium salt derivative is successfully prepared by modifying the structure of pleuromutilin C and then modifying the structure of pleuromutilin C by using a bromomethyl aromatic compound. In-vitro antibacterial activity determination proves that the compound has good in-vitro antibacterial activity and strong mycoplasma inhibiting activity, and has good antibacterial activity on pathogenic microorganisms. Meanwhile, the compound can combine with a novel allosteric pocket on a pathogenic microorganism related target, induce conformation remodeling and expansion of a neighboring active pocket, promote further occupation of the compound on the active pocket, and improve the antibacterial activity. Therefore, the compound can improve the poor solubility problem of the truncated pleuromutilin derivative, and can be developed and applied as a potential antibacterial drug.

A compound selected from 14-O-[((Alkyl-, cycloalkyl-, heterocycloalkyl-, heteroaryl-, or aryl)-sulfanyl)-acetyl]-12-epi-mutilins, or 14-O-[((Alkyl-, cycloalkyl-, heterocycloalkyl-, heteroaryl-, or aryl)-oxy)-acetyl]-12-epi-mutilins, wherein 12-epi-mutilin is characterized in that the mutilin ring at position 12 is substituted by two substituents, the first substituent at position 12 of the mutilin ring is a methyl group which methyl group has the inverse stereochemistry compared with the stereochemistry of the methyl group at position 12 of the naturally occurring pleuromutilin ring, the second substituent at position 12 of the mutilin ring is a hydrocarbon group comprising at least one nitrogen atom and all other substituents of the mutilin ring having the same stereochemistry compared with the stereochemistry of the substituents at the corresponding positions in the naturally occurring pleuromutilin ring; optionally in the form of a pharmaceutically acceptable salt and / or solvate, prodrug or metabolite, wherein the naturally occurring pleuromutilin is of formula.for the specific use in the treatment or prevention of a disease mediated by a virus. The invention further relates to 12-epi-12-desvinyl-14-O-[(Piperidin-4-ylsulfanyl]-acetyl]-12-[2-(3-methyl-pyrazin-2-yl)-ethenyl]-mutilin and its therapeutic uses.

The invention relates to an ether-containing pleuromutilin derivative as well as a preparation method and application thereof. The structural formula of the pleuromutilin derivative is shown as a formula Y. An antibacterial activity test on the pleuromutilin derivative containing ethers proves that the pleuromutilin derivative containing ethers has relatively good antibacterial activity on Xanthomonas oryzae pv. Oryzae, Pseudomonas oryzae pv. Oryzae and Xanthomonas citri pv. Citri. And the preparation method is simple, and the production cost is low.

This invention provides a preparation process for tiamulin fumarate, belonging to the field of compound synthesis technology, comprising the following steps: truncated pleuromedullary is reacted with a bifunctional solid organic base and 2,4,6-trimethylbenzenesulfonyl chloride in a mixed solvent A to obtain a concentrated intermediate of truncated pleuromedullary trimethylbenzenesulfonate; 2-diethylaminochloroethane hydrochloride is deacidified in a fixed bed packed with a bifunctional solid organic base, reacted with sodium thiosulfate, and exchanged with tetrabutylammonium bromide to obtain 2-diethylaminoethyl Bunte salt tetrabutylammonium salt; after the reaction, the two react with fumaric acid to form a salt crystallization, yielding tiamulin fumarate. This invention can improve the reaction efficiency and selectivity of the truncated pleuromedullary sulfonation reaction, and further improve the yield and content of tiamulin fumarate.

The present invention relates to a pleuromutilin wettable powder and a method for preparing the same. The pleuromutilin wettable powder contains 5-25 wt% pleuromutilin, 2-6 wt% wetting and dispersing agent, and the remainder a filler. The raw materials are pulverized in an airflow mill to a particle size of less than 325 mesh to obtain a 5-25% pleuromutilin wettable powder. The 5-25% pleuromutilin wettable powder can be used to prevent and treat various agricultural diseases, such as the pathogen of rice bacterial leaf blight.

This invention belongs to the field of pesticide technology, specifically relating to a truncated pleurotin compound, its preparation method, fungicidal composition, and application. The compound is shown in general formula I: wherein R1 represents alkyl, alkenyl, or alkynyl, and R1 is not methyl; R2 represents hydrogen, halogen, alkyl, alkenyl, alkynyl, or alkoxy; R8 represents hydrogen, alkyl, alkenyl, or alkynyl; and R3, R4, R5, R6, and R7 independently represent hydrogen, halogen, alkyl, alkenyl, etc. The compound exhibits good control activity against various types of fungi and bacteria.

The invention provides a pleuromutilin derivative containing a thioacetate side chain and application of the pleuromutilin derivative in prevention and treatment of plant diseases. The pleuromutilin derivative is a compound represented by a formula I, or a stereoisomer, a tautomer, an isotope derivative and a pesticide acceptable salt thereof. The pleuromutilin derivative disclosed by the invention shows excellent bacteriostatic activity on phytopathogens such as pathogenic bacteria, and particularly shows a remarkable inhibition effect on xanthomonas pathogenic bacteria and Releiella pathogenic bacteria, and particularly on Xanthomonas oryzae pv. Oryzae and Xanthomonas citri pv. Citrullis pv. Citrullis pv. Citrullis pv. Citrullis pv. Citrullis. The pleuromutilin derivative is low in preparation difficulty, and raw materials are cheap and easy to obtain. Therefore, the compound has further development value and is expected to be developed into a novel agricultural bactericide. Formula I

The invention provides a pleuromutilin derivative containing an amino side chain and application of the pleuromutilin derivative in prevention and treatment of plant diseases. The pleuromutilin derivative is a compound represented by a formula I, or a stereoisomer, a tautomer, an isotope derivative and a pesticide acceptable salt thereof. The pleuromutilin derivative disclosed by the invention shows excellent bacteriostatic activity on phytopathogens such as pathogenic bacteria, and particularly shows a remarkable inhibition effect on xanthomonas pathogenic bacteria and Releiella pathogenic bacteria, and particularly on Xanthomonas oryzae pv. Oryzae and Xanthomonas citri pv. Citrullis pv. Citrullis pv. Citrullis pv. Citrullis pv. Citrullis. The pleuromutilin derivative is low in preparation difficulty, and raw materials are cheap and easy to obtain. Therefore, the compound has further development value and is expected to be developed into a novel agricultural bactericide. Formula I.

The invention relates to a thioether-containing pleuromutilin derivative as well as a preparation method and application thereof. The structural formula is shown as a formula H. An antibacterial activity test on the thioether-containing pleuromutilin derivative proves that the thioether-containing pleuromutilin derivative has good antibacterial activity on Xanthomonas oryzae pv. Oryzae, Pseudomonas oryzae pv. Oryzae and Xanthomonas citri pv. Citri. And the preparation method is simple, and the production cost is low.

This invention discloses a truncated pleurotin derivative, its preparation method, and its application, belonging to the field of pharmaceutical chemistry. The compound is synthesized in two steps: starting with furfural, via a thiolation reaction followed by a substitution reaction with truncated pleurotin. The final product is obtained by recrystallization in a mixed solvent. This synthetic method is low-cost, safe to operate, and suitable for industrial production. Preliminary bioactivity tests show that the compound has good activity against Staphylococcus aureus, drug-resistant Staphylococcus aureus, and Staphylococcus intermedius, making it a promising novel antibacterial drug for the prevention and treatment of infectious diseases caused by Staphylococcus aureus and Staphylococcus intermedius in humans and / or animals. The structural formula (I) of the truncated pleurotin derivative is:

The present invention belongs to the technical field of pesticides and specifically relates to a pleuromutilin compound, a preparation method therefor, and an antimicrobial composition and use thereof. The compound is represented by general formula I, where R1 represents alkyl, alkenyl, or alkynyl, and R1 is not methyl; R2 represents hydrogen, halogen, alkyl, alkenyl, alkynyl, or alkoxy; R8 represents hydrogen, alkyl, alkenyl, or alkynyl; and R3, R4, R5, R6, and R7 each independently represent hydrogen, halogen, alkyl, alkenyl, or the like. The compound exhibits good control activity against various fungi and bacteria.

The application belongs to the technical field of medicine, and discloses a kind of amidine compound and its preparation method and application in treating bacterial infection, specifically discloses a kind of amidine compound and its pharmaceutically acceptable salt and preparation method and application in treating bacterial infection as shown in the following general formula (I).The amidine compound of the application is used in the preparation of products for enhancing the activity of other antibiotics.The antibiotics include macrolide drugs, pleuromutilin drugs, quinolone drugs, rifamycin drugs, dihydrofolate reductase inhibitor drugs, oxazolidinone drugs, lincosamide drugs, capreomycin drugs, mupirocin drugs and fusidic acid drugs.

The invention provides a pleuromutilin derivative containing a thioether side chain and application of the pleuromutilin derivative in prevention and treatment of plant diseases. The pleuromutilin derivative is a compound represented by a formula I, or a stereoisomer, a tautomer, an isotope derivative and a pesticide acceptable salt thereof. The pleuromutilin derivative disclosed by the invention shows excellent bacteriostatic activity on phytopathogens such as pathogenic bacteria, and particularly shows a remarkable inhibition effect on xanthomonas pathogenic bacteria and Releiella pathogenic bacteria, and particularly on Xanthomonas oryzae pv. Oryzae, Xanthomonas citri pv. Citri and Pseudomonas solanacearum pv. Lanceolatifolia pv. Lanceolatifolia pv. Lanceolatifolia pv. Lanceolatifolia. The pleuromutilin derivative is low in preparation difficulty, and raw materials are cheap and easy to obtain. Therefore, the compound has further development value and is expected to be developed into a novel agricultural bactericide. Formula I.

The invention belongs to the field of medicinal chemistry, and discloses an aromatic pleuromutilin derivative with an antibacterial effect as well as a preparation method and application of the aromatic pleuromutilin derivative. The pleuromutilin is structurally modified, aromatic group modification is further increased through a reductive amination method after mercaptoethylamine is introduced into a C-14 side chain, and the structural formula of the pleuromutilin is shown in the specification. Research on an antibacterial mechanism finds that the series of derivatives can effectively interfere with expression of bacterial protein and show unique and excellent antibacterial activity, and the pleuromutilin can be applied to preparation of antibacterial agents. Compared with pleuromutilin in the prior art, most of the pleuromutilin compounds have antibacterial activity on staphylococcus aureus, escherichia coli, salmonella, micrococcus luteus and enterococcus faecalis which are common in in-vitro clinical application, hardly generate drug resistance, have stable safety and are expected to be further optimized into lead compounds of novel antibiotics.

The invention discloses a hematopoietic stem cell activator injection containing plerixafor and a preparation method thereof, and belongs to the technical field of medicines. Aiming at the problems of low dissolution efficiency, insufficient stability, risk of organic solvent residue and the like in the development of a plerixafor preparation, the preparation method comprises the following steps: dissolving plerixafor in a hydrochloric acid-organic solvent system to realize synergistic pre-dissolution, adding citric acid to form a stable compound, and carrying out reduced pressure rotary evaporation to remove the organic solvent. According to the injection and the preparation method thereof, the dissolution time and the process time are remarkably shortened, the stability of the preparation can be effectively enhanced, the clinical adverse reaction risk is reduced, and the injection is suitable for clinical application related to hematopoietic stem cell transplantation.

The invention belongs to the technical field of organic synthesis, and particularly relates to a preparation method of novel tiamulin fumarate. The preparation method comprises the following steps: reacting pleuromutilin with thionyl chloride to generate chlorinated pleuromutilin; reacting the chlorinated pleuromutilin with thiourea, and carrying out alkali treatment, so as to generate sulfhydrylated pleuromutilin; the preparation method comprises the following steps: reacting sulfhydrylated pleuromutilin with 2-bromo-N, N-diethyl ethyl-1-amine to form tiamulin, and finally carrying out a salt forming reaction. The invention provides a synthetic route of chlorination, sulfhydrylation, alkylation and salification, and two key intermediates, namely the chlorinated pleuromutilin and the sulfhydrylated pleuromutilin, are prepared step by step, so that the accurate control of the reaction process is realized. Wherein the chlorination reaction is catalyzed by N, N-dimethylaniline, the low-temperature staged reaction is adopted, and the selectivity is good; thiourea is used for alkaline hydrolysis in sulfhydrylation, so that foul mercaptan is avoided; alkylation is carried out under weak base and low temperature; no controlled reagent is needed in the whole process, and green chemical requirements are met.

The application belongs to the technical field of medicine, and discloses a kind of amidine compound and its preparation method and application in treating bacterial infection, specifically discloses a kind of amidine compound and its pharmaceutically acceptable salt and preparation method and application in treating bacterial infection as shown in the following general formula (I).The amidine compound of the application has the use in preparing the product for enhancing the activity of other antibiotics.The antibiotics include macrolide drugs, pleuromutilin drugs, quinolone drugs, rifamycin drugs, dihydrofolate reductase inhibitor drugs, oxazolidinone drugs, lincosamide drugs, capreomycin drugs, mupirocin drugs and fusidic acid drugs.

The invention relates to the technical field of antibacterial drugs, and particularly discloses a pleuromutilin derivative and application thereof, and the pleuromutilin derivative is structurally characterized in that flavanone or an oximido / oxime ether derivative of flavanone is connected to a side chain of pleuromutilin C14 through mercaptoethylamine, piperazine or an oxygen atom. According to the invention, pleuromutilin is taken as a raw material, flavanone (naringenin and hesperetin) with an antibacterial effect and an oximido / oxime ether derivative thereof are introduced into a pleuromutilin C14 side chain, and the flavanone and the oximido / oxime ether derivative thereof show huge potential as a dominant structural unit due to a specific C6-C3-C6 basic skeleton (C2 and C3 sites are single bonds) and wide antibacterial activity; the flavonoid compound is combined with pleuromutilin to synthesize a plurality of dihydroflavonoid pleuromutilin derivatives with excellent antibacterial activity, and a new choice is provided for designing a new generation of pleuromutilin derivatives through a hybridization strategy, improving the drug characteristics of the pleuromutilin derivatives while improving the activity and anti-infection drugs of the pleuromutilin derivatives.