14 results about "Epoxide metabolism" patented technology

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 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.

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.

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.

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.

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 application relates to a kind of sulfonylurea compounds as shown in formula I, preparation method and its application.The compound of the present application has soluble epoxide hydrolase (sEH) inhibitory activity, can increase the level of epoxyeicosatrienoic acid (EETs), and then reduce inflammatory response, can be used for the prevention and treatment of heart failure.The preparation method of the present application has the technical advantages of simple steps, high yield and easily available raw materials.

This invention discloses a method for preparing (R)-tebuconazole epoxide intermediates using an epoxide hydrolase mutant, belonging to the field of biocatalysis technology. The preparation of chiral tebuconazole single enantiomers is limited by separation and asymmetric synthesis techniques, making large-scale production impossible. This invention provides a recombinant strain *E. coli* / Rpeh expressing a *Rhodotorula paludinis* epoxide hydrolase mutant. M Using whole cells as catalysts, the 200 mM racemic epoxy intermediate was hydrolyzed and resolved under the conditions of 30 °C and pH 7.5, yielding an ee value of 84% and a yield of 28.9% for the preparation of (R)-tebuconazole epoxy intermediate. This method has advantages such as mild reaction conditions, environmentally friendly catalytic activity, high product optical purity, and high substrate tolerance. It provides other key chiral prerequisites for the preparation of (R)-tebuconazole single enantiomers and has the potential for industrial application.

This application discloses an epoxide hydrolase gene cloned from Angelica dahurica. AdEH1 and AdEH2 and its encoded proteins and applications, among which, AdEH 1 and AdEH2 The nucleotide sequences are shown in SEQ ID NO: 1 and SEQ ID NO: 2, respectively, and the amino acid sequences encoding the proteins are shown in SEQ ID NO: 3 and SEQ ID NO: 4, respectively. AdEH1 and AdEH2 The encoded protein possesses epoxide hydrolase catalytic activity, capable of catalyzing the oxidation of imperatorin and angelica root to produce hydrated oxidized imperatorin and angelica root. This application identifies the gene. AdEH1 and AdEH2 Its key role in the biosynthesis of furanocoumarins provides core gene resources for the regulation and green large-scale synthesis of furanocoumarin components in Angelica dahurica, and also provides technical support for the accurate detection of related compounds.

The invention provides a urea derivative as well as a preparation method and application thereof, and belongs to the field of medicines. The urea derivative provided by the invention has a typical urea structure as a primary pharmacophore of soluble epoxide hydrolase (sEH), can stabilize an endogenous substance epoxy fatty acid with wide physiological activity, and has a very strong inhibition effect on human recombinant sEH; the traditional Chinese medicine composition can regulate the generation of various proinflammatory cytokines, relieve endoplasmic reticulum stress, prevent or reverse endothelial dysfunction and stabilize mitochondria.

This invention relates to the field of pharmaceutical technology, providing memantine derivatives, their preparation methods, and their application in the preparation of drugs for treating soluble cyclooxygenase-mediated diseases. The memantine derivatives provided by this invention have typical urea or amide structures. The urea and amide structures serve as the primary pharmacophores of sEH (hydrophobic epoxide hemoglobin). The memantine moiety, as a hydrophobic segment, interacts with the receptor hydrophobically. Molecular docking shows that the memantine moiety, as a hydrophobic segment, interacts with the receptor hydrophobically, particularly when both R1 and R2 are methyl groups, which enhances the van der Waals forces. Therefore, the memantine derivatives provided by this invention exhibit high inhibitory activity against human (HsEH) and murine sEH (MsEH), and can be used as sEH inhibitors in the preparation of drugs for treating soluble cyclooxygenase-mediated diseases, showing broad application prospects.

This invention discloses an epoxide hydrolase mutant, biomaterials, products, and applications. Compared to the wild-type epoxide hydrolase, this mutant possesses one or more amino acid residue mutations at positions 108, 131, and 256. The catalytic activity of this series of mutants is significantly improved compared to the wild-type enzyme, with the most preferred mutant being F108V / D131N / E256V. (S) - Epoxyphenylethane formation (S) When synthesizing 1,2-ethylene glycol, the yield can reach 93% under optimal reaction conditions. Furthermore, the reaction conditions for the catalytic synthesis of chiral 1,2-ethylene glycol using this series of mutants are mild, and the production process is environmentally friendly, demonstrating excellent industrial application value.