93 results about "Epoxide metabolism" patented technology

The invention relates to the technical field of bioengineering and fine chemical engineering, in particular to epoxide hydrolase, a gene, a carrier, engineering bacteria and application, and the amino acid sequence of the epoxide hydrolase is shown as SEQ ID NO.3. The epoxide hydrolase disclosed by the invention has the advantages that the epoxide hydrolase is Sphingopyis macrogoltabia EY-1, and the structural formula of the epoxide hydrolase is as shown in the specification. According to the invention, a recombinant plasmid pET-28a-smh containing an optimized gene and a genetic engineering bacterium E.coli / smh are constructed, the engineering bacterium is induced to over-express the recombinant epoxide hydrolase SmEH, and the recombinant epoxide hydrolase SmEH has catalytic activity. According to the present invention, the E.coli / smh whole cell is adopted to respectively catalyze the hydrolysis reaction of the (R)-styrene oxide (SO) and the (S)-styrene oxide (SO) so as to obtain the (R)-styrene oxide (SO) and the (S)-1, 2-phenyl glycol (1-Phenyl-1, 2-ethanediol, PED) with high optical purity, and the application of the E.coli / smh whole cell to respectively catalyze the hydrolysis reaction of the (R)-styrene oxide (SO) and the (S)-1, 2-phenyl glycol (1-Phenyl-1, 2-ethanediol, PED) is provided;

A first aspect of the invention relates to a method of treating or preventing tissue damage, or treating or preventing tissue destruction, in a subject, said method comprising administering to the subject a therapeutically or prophylactically effective amount of a soluble epoxide hydrolase (sEH) inhibitor. A further aspect of the invention relates to a method of treating or preventing leishmaniasis in a subject, said method comprising administering to the subject a therapeutically or prophylactically effective amount of a soluble epoxide hydrolase inhibitor.

Compounds (I) are provided, where R1 and R2 are H or (C1-C3)-alkyl; X is a linear methylene chain of formula —[CH2]n— with n=0, 1 or 2, or a biradical from a branched saturated (C2-C4)-alkylene chain; and A is either a C-radical from a non-aromatic polycyclic 6- to 15-membered carbocyclic ring system, or a C-radical from a polycyclic 6- to 15-membered heterocyclic ring system having one or two O, S or N; wherein the C-radicals are unsubstituted or substituted. Compounds (I) are simultaneously inhibitors of soluble epoxide hydrolase and inhibitors of glutaminyl cyclase. Besides, they reduce the levels of pro-inflammatory cytokines in LPS stimulated BV2 cells, display low cytotoxicity, and have good BBB permeability. Thus, they are useful as multitarget compounds for the prevention or treatment of Alzheimer's disease.

The invention discloses application of heart washing soup in preparation of a medicine for reducing soluble epoxide hydrolase in liver. The heart washing decoction disclosed by the invention can regulate and control soluble epoxide hydrolase and 14, 15-epoxy eicosatrienoic acid, and can improve central neuron insulin resistance, so that diabetes mellitus can be treated, and symptoms of Alzheimer disease can be improved.

The present invention discloses the construction and application of a recombinant Gluconobacter oxydans, belonging to the fields of genetic engineering and whole-cell catalysis. The present invention heterologously expresses an epoxide hydrolase from Sphingomonas in Gluconobacter oxydans, and simultaneously utilizes the alcohol and aldehyde dehydrogenases bound to the membrane of Gluconobacter oxydans itself to synthesize R-mandelic acid in a one-step process using styrene oxide as a substrate. The present invention combines the transcriptome data of Gluconobacter oxydans, screens 7 strong promoters using green fluorescent protein as a reporter gene, and determines the strongest promoter P for expressing the epoxide hydrolase gene. 12780 , ultimately significantly increasing the yield of R-mandelic acid.

To provide methods of producing new sweetening compounds improved in taste and delivery characteristics, and recombinant cells.SOLUTION: A method of producing a compound 1 comprises: contacting mogroside IIIE with a recombinant host cell that comprises a first enzyme catalyzing the production of the compound 1 from the mogroside IIIE, where the recombinant host cell comprises a cytochrome P450, a glycosylating enzyme and / or an epoxide hydrolase of specific sequences, and where the first enzyme is one or more of cyclomaltodextrin glucanotransferases, dextransucrases, and dextranases.SELECTED DRAWING: Figure 42

The invention belongs to the technical field of medicinal chemistry, and discloses a modular preparation method and application of a protein degradation agent targeting soluble epoxide hydrolase (sEH). The derivative has a structural general formula as shown in a formula (I), wherein X and Y substituent groups can be randomly combined. The compound can effectively degrade sEH level in cells and living bodies, and shows a remarkable protective effect on acute liver inflammation of mice in the living bodies. Particularly, the compound shows excellent degradation activity (EC50 = 2.9 nM) in 1d, can quickly relieve acute inflammation induced by LPS, and can be used for research and development of drugs for acute inflammation related diseases.

The present application relates to an aromatic-substituted benzimidazole compound, a cis-trans isomer, a hydrate, a solvate, a pharmaceutically acceptable salt or a prodrug thereof. The present application also relates to a method for preparing an aromatic-substituted benzimidazole compound, and the use of the aromatic-substituted benzimidazole compound as a soluble epoxide hydrolase inhibitor. The aromatic-substituted benzimidazole compounds described herein exhibit extremely high inhibitory activity against soluble epoxide hydrolase, with IC 50 values in the nanomolar range or even lower.

The present invention relates to a sulfonylurea compound represented by formula I, a preparation method therefor, and an application thereof. The compound of the present invention have soluble epoxide hydrolase (sEH) inhibitory activity and can increase the level of epoxyeicosatrienoic acids (EETs)so as to alleviate inflammatory responses, and thus can be used for preventing and treating heart failure. The preparation method of the present invention has the technical advantages of simple steps, high yield, and easily available raw materials.

The present invention relates to the technical field of compound synthesis, and more specifically, to a compound containing benzothiazole or benzoxazole, a preparation method thereof, and an application thereof. The structural formula of the compound containing benzothiazole or benzoxazole is as follows: wherein Y represents O or S, X represents hydrogen or halogen, and R represents any one of a substituted or unsubstituted C3-C8 cycloalkyl, a substituted or unsubstituted phenyl, a substituted or unsubstituted C1-C10 alkyl, and a substituted or unsubstituted C3-C10 alkenyl. The compound can be used as a soluble epoxide hydrolase inhibitor, thereby having a certain therapeutic effect on diseases caused by soluble epoxide hydrolase disorders.

Provided herein are methods of preventing, suppressing, or treating cancer cachexia in a subject as well as methods of prolonging survival of a subject in need of cancer cachexia treatment. Such methods include administering an inhibitor of soluble epoxide hydrolase (sEH).

Described herein are novel piperidine urea derivative compounds and pharmaceutical compositions thereof for the treatment of neurodegenerative disorders and diseases mediated by soluble epoxide hydrolases.

The present application relates to PET imaging of soluble epoxide hydrolase (sEH) 18 F-FNDP. Disclosed herein are radiofluorinated FNDPs for PET imaging of soluble epoxide hydrolase (sEH) and methods of use thereof, in particular, compounds of Formula (I) of the present application and uses thereof are disclosed.

The invention relates to a heteroaryl or phenyl imidazole compound containing an aromatic substituent group, and a stereoisomer, a hydrate, a solvate, a pharmaceutically acceptable salt or a prodrug of the heteroaryl or phenyl imidazole compound. The invention also relates to a preparation method of the heteroaryl or phenyl imidazole compound containing the aromatic substituent group, and application of the heteroaryl or phenyl imidazole compound containing the aromatic substituent group as a soluble epoxide hydrolase inhibitor. The aromatic substituent group-containing heteroaryl or phenyl imidazole compound disclosed by the invention shows extremely high inhibitory activity on soluble epoxide hydrolase, and the IC50 value is at the nanomole level or even lower.

This invention provides a berberine derivative, a pharmaceutical composition, and its application, relating to the field of medicinal chemistry. The main skeleton of the berberine derivative is berberine with a urea group. By connecting different substituents to different sites on the berberine skeleton through the urea group and changing the oxidation state of the C ring, a series of berberine derivatives with high activity against soluble epoxide hydrolase were obtained. The IC50 value of the berberine derivatives inhibiting soluble epoxide hydrolase reaches the nanomolar level, indicating that the berberine derivatives have a highly efficient inhibitory effect on soluble epoxide hydrolase. Thus, by inhibiting soluble epoxide hydrolase, an anti-inflammatory effect can be achieved, which has good application scenarios.

The invention discloses application of epoxy hydrolase derived from rhodosporidium toruloides in asymmetric synthesis of epoxide intermediates, and belongs to the technical field of bioengineering. According to the method, firstly, recombinant bacteria E.coli / Rteh for expressing epoxy hydrolase derived from rhodosporidium toruloides are used as a whole-cell catalyst, and characterization analysis is carried out on 12 substrates, so that the enzyme has catalytic activity on various epoxides. The (R)-tebuconazole epoxy intermediate with high enantiomer purity (ee = 76.8%) can be obtained in the chiral resolution reaction of the E.coli / Rteh whole-cell catalysis racemization tebuconazole epoxy intermediate, and the yield is 33.1%. The method has the advantages of mild reaction conditions, environmental friendliness, high catalytic activity, high optical purity of the product and the like, and has important application prospects.

The invention provides a glycyrrhetinic acid derivative, a pharmaceutical composition and application of the glycyrrhetinic acid derivative and relates to the technical field of pharmaceutical chemistry, a main framework of the prepared glycyrrhetinic acid derivative is glycyrrhetinic acid with carbamido, and the glycyrrhetinic acid derivative with the carbamido is obtained by modifying the 3-site, 11-site, 18-site and 30-site of the glycyrrhetinic acid and modifying the 3-site, 11-site, 18-site and 30-site of the glycyrrhetinic acid. Therefore, the compound has nanomole-level inhibitory activity on soluble epoxide hydrolase. On the basis of 18alpha / 18beta-glycyrrhetinic acid, different ureido substituents are introduced to the 30th site, the activity difference between the different substituents is small, but when the different ureido substituents are connected to the 20th site of the 18alpha / 18beta-glycyrrhetinic acid, the inhibition effect of the 18alpha / 18beta-glycyrrhetinic acid on soluble epoxide hydrolase is greatly reduced. The glycyrrhetinic acid derivative prepared by the invention has an efficient inhibition effect on soluble epoxide hydrolase, so that the inhibition effect on inflammation can be realized by inhibiting the soluble epoxide hydrolase, and the glycyrrhetinic acid derivative has a good application prospect.

Compounds (I) are provided, wherein R1 and R2 are H or (C1-C3)-alkyl; x is a linear methylene chain of formula-[CH2] n-, n = 0, 1 or 2, or is a divalent group of a branched saturated (C2-C4)-alkylene chain; and A is a C-group from a non-aromatic polycyclic 6 to 15 membered carbocyclic system, or a C-group from a polycyclic 6 to 15 membered heterocyclic system having one or two of O, S or N; wherein the C-group is unsubstituted or substituted. Compound (I) is both an inhibitor of soluble epoxide hydrolase and an inhibitor of glutaminyl cyclase. In addition, compound (I) reduces the level of pro-inflammatory cytokines in LPS-stimulated BV2 cells, shows low cytotoxicity and has good BBB permeability. Therefore, they are useful as multi-target compounds for the prevention or treatment of Alzheimer's disease.

The invention discloses a method for preparing (R)-styrene oxide based on epoxide hydrolase, which comprises the following steps: carrying out enzyme catalysis reaction in a biphase system under the action of epoxide hydrolase by taking a racemic ethylene oxide compound as a substrate to obtain (R)-styrene oxide and (R)-1-phenyl-1, 2-ethylene glycol or (S)-1-phenyl-1, 2-ethylene glycol; the temperature of the enzyme catalytic reaction is controlled to be 5-50 DEG C, and the reaction time is 2-24 hours. According to the method, the racemic ethylene oxide compound can be efficiently split with high stereoselectivity, the enzyme catalysis effect is good, and the optical purity of the product is high.

The present disclosure provides a recombinant host system for producing 9,10,16-trihydroxyhexadecanoic acid (aleuritic acid), wherein the host system is transformed with: (i) a first recombinant expression vector comprising nucleic acid sequences encoding the desaturase enzyme and the epoxygenase enzyme, and a second recombinant expression vector comprising nucleic acid sequences encoding the epoxide hydrolase enzyme and the monooxygenase enzyme, or (ii) a first recombinant expression vector comprising nucleic acid sequences encoding the desaturase enzyme and the bifunctional epoxygenase hydrolase enzyme, and a second recombinant expression vector comprising a nucleic acid sequence encoding the monooxygenase enzyme. The present disclosure further provides methods for producing aleuritic acid using the recombinant host system.

The present invention relates to potent soluble epoxide hydrolase inhibitors. The present invention discloses a series of novel soluble epoxide hydrolase (sEH) inhibitors with improved physical properties that enhance the drug-like properties of the soluble epoxide hydrolase inhibitors for treating sEH-related diseases such as chronic diabetic neuropathic pain.

This invention discloses a method for preparing 1,2-pentanediol, comprising using 2-pentanone as a substrate, adding 2-keto reductase, linalool dehydratase, formate dehydrogenase, lysozyme, coenzyme NAD+, and water to react and obtain n-pentene. The obtained n-pentene is then thoroughly mixed with ethanol. This mixture is then fed into a reaction system containing olefin monooxygenase, epoxide hydrolase, formate dehydrogenase, lysozyme, coenzyme NAD+, MgSO4, and water using a fed-batch method. After the n-pentene and ethanol mixture has been completely added, the reaction continues for a period of time, followed by extraction to obtain 1,2-pentanediol. This preparation method uses 2-pentanone as a raw material, catalyzing the synthesis of 2-pentanol via 2-keto reductase. 2-pentanol is then catalyzed by a dehydrating enzyme to generate n-pentene, which is then catalyzed by an olefin monooxygenase to generate 1,2-epoxypentane. Finally, epoxide hydrolase ring-opens the 1,2-pentanediol. This process requires only four enzymatic catalytic reactions for efficient synthesis.

The application provides a glycyrrhetinic acid derivative, a pharmaceutical composition and application thereof, relates to the technical field of medicinal chemistry, and the main skeleton of the glycyrrhetinic acid derivative prepared by the application is glycyrrhetinic acid with a urea group; the 3th position, the 11th position, the 18th position and the 30th position of the glycyrrhetinic acid are modified, so that the glycyrrhetinic acid derivative has nanomolar level inhibitory activity on soluble epoxide hydrolase. Different urea group substituents are introduced into the 30th position on the basis of 18alpha / 18beta-glycyrrhetinic acid, and the activity difference between different substituents is small, but when different urea group substituents are connected to the 20th position of 18alpha / 18beta-glycyrrhetinic acid, the inhibitory effect of the glycyrrhetinic acid derivative on soluble epoxide hydrolase is greatly reduced. The glycyrrhetinic acid derivative prepared by the application has high inhibitory effect on soluble epoxide hydrolase, so that the inhibitory effect on inflammation can be realized by inhibiting soluble epoxide hydrolase, and the glycyrrhetinic acid derivative has good application prospect.

Provided is a method for constructing an engineered yeast for de novo synthesis of mogroside. The method comprises: inserting constructed cucurbitadienol synthase gene expression cassette Ptef1-cds-Tcyc1, epoxide hydrolase gene expression cassette Ptef1-eph3-Tcyc1, cytochrome P450 enzyme-encoding gene CYP and cytochrome P450 enzyme reductase gene expression cassette Ttdh3-cyp87d18-P gal1 / 10-atcpr2-Tcyc1, and glycosyltransferase-encoding gene expression cassette Tadh1-ugt74ac1-Pgal1 / 10-ugtms1-Tcyc1 into a yeast genome, so as to obtain an engineered yeast for mogroside production. The engineered yeast can be used for de novo synthesis of mogroside by using glucose as a substrate for fermentation.

The invention discloses an epoxide hydrolase mutant and a construction method and application of a co-immobilized enzyme of the epoxide hydrolase mutant. The inventor firstly constructs a recombinant expression vector of epoxide hydrolysis MdEH, then constructs a recombinant expression vector of point mutation MdEH-K71I on the basis, then constructs an MdEH-K71I recombinant expression vector suitable for being used in bacillus subtilis, and then replaces a promoter and a signal peptide in the expression vector. The modified recombinant expression vector is used for transforming bacillus subtilis, so that efficient secretory expression of the epoxide hydrolase in a bacillus subtilis expression system is realized. The process conditions of co-immobilization of epoxide hydrolase and halohydrin dehalogenase are further explored, ECR8285 resin is selected as an immobilization carrier, and the conversion rate of glycerin generated by hydrolysis finally reaches 80.29%.

A first aspect of the invention relates to a method of treating or preventing tissue damage, or treating or preventing tissue destruction, in a subject, said method comprising administering to the subject a therapeutically or prophylactically effective amount of a soluble epoxide hydrolase (sEH) inhibitor. A further aspect of the invention relates to a method of treating or preventing leishmaniasis in a subject, said method comprising administering to the subject a therapeutically or prophylactically effective amount of a soluble epoxide hydrolase inhibitor.

A fusion protein and an immobilized enzyme including the fusion protein are provided. The fusion protein includes an epoxide hydrolase active domain and a chitin protein binding domain. Efficient immobilization of epoxide hydrolase is achieved through the specific affinity between chitin and the fusion protein, and ethylhexyl glycidyl ether is used as a substrate to efficiently produce ethylhexylglycerin with the immobilized enzyme. The immobilization method offers advantages such as low cost, high enzyme immobilization efficiency, minimal enzyme activity loss, and strong specificity, fundamentally solving issues like poor recyclability and low stability of free enzymes, as well as low repeatability in traditional whole-cell immobilization methods. It resolves issues such as deep color and protein residues in downstream separation and purification.

The present invention relates to compounds of formulae I and II. The compounds are useful for treating hypertension, atherosclerosis, pulmonary diseases, diabetes, pain, fibrosis, addictive disorders, inflammation, and immunological disorders or a condition treatable or preventable by inhibition of soluble epoxide hydrolase. Preferred compounds are N-((adamantan-1-yl)carbamoyl)-benzenesulfonamide derivatives. Exemplary compounds are e.g. •N—(((1r,3s,5R,7S)-3-hydroxyadamantan-1-yl)carbamoyl)-4-methylbenzenesulfonamide (example 14, compound 4a) •4-(tert-butyl)-N—(((1r,3s,5R,7S)-3-hydroxyadamantan-1-yl)carbamoyl)benzenesulfonamide (example 15, compound 4b) •N—(((1r,3s,5R,7S)-3-hydroxyadamantan-1-yl)carbamoyl)-4-(trifluoromethyl)benzenesulfonamide (example 16, compound 4j). The present description discloses the synthesis and characterisation of exemplary compounds as well as pharmacological data thereof.

The application provides a stilbene compound, a pharmaceutical composition and application thereof, relates to the technical field of medicinal chemistry, and the main skeleton of the compound is a stilbene with a urea group; a series of high-activity stilbene compounds are obtained by expanding different substituents on both sides of the urea group and synthesizing a stilbene side skeleton containing an advantage structure of a natural product; the IC50 value of the high-activity stilbene compound to soluble epoxide hydrolase inhibition reaches the nanomolar level, indicating that the stilbene compound has a high inhibition effect on soluble epoxide hydrolase inhibition enzyme, so that the inhibition effect on inflammation can be realized by inhibiting soluble epoxide hydrolase inhibition enzyme, and the stilbene compound has a good application prospect.

The present invention discloses an epoxide hydrolase mutant and its application in asymmetric synthesis ( S The present invention relates to the application of )-flutriafol epoxy intermediates in the field of enzyme engineering technology. The present invention obtains an epoxide hydrolase mutant with improved enantioselectivity by site-directed mutagenesis of epoxide hydrolase. Rp EH H336W / L360F Compared with the wild type, the epoxide hydrolase mutant Rp EH H336W / L360F right rac The enantioselectivity of the flutriafol epoxy intermediate is significantly improved. Compared with expensive chiral chromatography separation methods, this method provides an environmentally friendly, simple process, and low-cost method for the synthesis of single enantiomers of flutriafol, which has great application prospects.