25 results about "Epoxide Hydrolases" 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 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.

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.

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.

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 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.

The invention provides a piperidinyl urea compound as shown in a formula (I), and the compound has efficient soluble epoxide hydrolase inhibitory activity and good in-vivo oral anti-inflammatory activity.

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.

The invention belongs to the technical field of biological catalysis, and particularly relates to a method for catalyzing hydrolysis of oxetane by using a series of epoxy hydrolase. According to the method, epoxy hydrolase in 23 databases is mined and represented through the technologies of gene mining, heterologous expression and the like, and it is determined that epoxy hydrolase and the like from metagenome DNA (Deoxyribonucleic Acid), Rhodococcus erythropolis, Rhodococcus subtilis, Actinomadura namibiensis and Rhodococcus aureus are adopted as catalytic enzymes, and the catalytic enzymes are used for catalyzing 2-phenyl oxetane to generate (S)-1-phenyl-1, 3-propylene glycol, so that the 2-phenyl oxetane can be used for catalyzing 2-phenyl oxetane to generate (S)-1-phenyl-1, 3-propylene glycol, and the application of the 2-phenyl oxetane to prepare the (S)-1-phenyl-1, 3-propylene glycol and the application of the 2-phenyl oxetane to prepare the (S)-1, 3-propylene glycol.

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.

This invention belongs to the field of pharmaceutical technology, specifically relating to a compound, its preparation method, and its application in the preparation of sEH inhibitors and PPARs agonists. This invention provides a compound having the structure shown in Formula II. The compound provided by this invention has a typical urea structure as the primary pharmacophore of soluble epoxide hydrolase (sEH), and a thiazolidinedione moiety as the primary pharmacophore of peroxisome proliferator-activated receptors (PPARs). The sEH inhibitor and PPARs agonist compound provided by this invention exhibits high inhibitory activity against human HsEH and high agonistic activity against PPARs, and can be used as an sEH inhibitor and PPARs agonist compound in the preparation of drugs for treating diseases mediated by soluble epoxide hydrolase and peroxisome proliferator-activated receptors.

The application belongs to the technical field of medicine, and particularly relates to a compound, a preparation method thereof and application of the compound in preparation of sEH inhibitors and PPARs agonists. The application provides a compound with a structure shown in formula V or VI. The compound provided by the application has a typical urea structure as a primary pharmacophore of soluble epoxide hydrolase (sEH) and a thiazolidinedione part as a primary pharmacophore of peroxisome proliferator-activated receptors (PPARs). The sEH inhibitor and PPARs agonist compound provided by the application has high inhibitory activity on human HsEH and high agonistic activity on PPARs, and can be used as an sEH inhibitor and PPARs agonist compound for preparation of a medicine for treating diseases mediated by soluble epoxide hydrolase and peroxisome proliferator-activated receptors.

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.

The present invention relates to soluble epoxide hydrolase (sEH) inhibitors of formula (I)to processes for their obtention and to their therapeutic indications.

Herein disclosed are compounds of formula (I), which are metabolized into, or act as, analogues of oncosterone (6-oxo-cholestan-3β,5α-diol), a metabolite produced by tumor cells overexpressing cholesterol-5,6-epoxide hydrolase (ChEH) and / or expressing 11β-hydroxysteroid dehydrogenase type 2 (HSD2) and the glucocorticoid receptor (GR), neutralizing the signaling pathway and tumorigenicity of oncosterone. The compounds of formula (I) herein disclosed are thus useful in preventing and / or treating cancers, in subjects, preferably humans, overexpressing cholesterol-5,6-epoxide hydrolase (ChEH) and / or expressing 11β-hydroxysteroid dehydrogenase type 2 (HSD2) and the glucocorticoid receptor (GR). In addition, being analogues of oncosterone, some of the compounds of formula (I) are also useful in the prevention and / or treatment of cancers expressing the glucocorticoid receptor (GR).

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.

The invention relates to compound synthesis, in particular to a preparation method of a soluble epoxide hydrolase (sEH) inhibitor t-TUCB (4-[(trin-4-{3-[4-(trifluoromethoxy) phenyl] ureido} cyclohexyl) oxy] benzoic acid). The preparation method comprises the following steps: carrying out an aromatic nucleophilic substitution reaction on trans-4-aminocyclohexanol or a corresponding salt thereof and p-fluorobenzonitrile under an alkaline condition to obtain 4-[(trin-4-aminocyclohexyl) oxy] benzonitrile (an intermediate I); the preparation method comprises the following steps: carrying out nucleophilic substitution reaction on p-trifluoromethoxyaniline and a carbonyl compound to obtain p-trifluoromethoxyphenyl isocyanate (an intermediate II); carrying out nucleophilic addition reaction on the intermediate I and the intermediate II to obtain 4-[(trin-4-{3-[4-(trifluoromethoxy) phenyl] ureido} cyclohexyl) oxy] cyanophenyl (intermediate III); the intermediate III is subjected to a hydrolysis reaction under the alkaline condition, and 4-[(trran-4-{3-[4-(trifluoromethoxy) phenyl] ureido} cyclohexyl) oxy] benzoic acid (t-TUCB) is obtained. The method has the advantages of high product quality, safe and stable production process, cheap and easily available starting materials and low production cost.