199 results about "Enzyme inhibitory" patented technology

Compositions comprising one or more practically insoluble proteasome inhibitors and a cyclodextrin, particularly a substituted cyclodextrin, substantially increase the solubility of these proteasome inhibitors and facilitate their administration. Such compositions optionally comprise a buffer. Methods of treatment using such compositions are also disclosed.

The compound represented by the general formula (I): wherein, a fused ring AB represents a 5- to 10-membered fused heterocyclic ring; R1 represents (1) a hydrogen atom, (2) a halogen atom, (3) a cyano group, (4) an oxo group, (5) an optionally protected hydroxyl group, (6) an optionally protected carboxyl group, (7) an optionally protected amino group, (8) a cyclic group which may have a substituent (s), (9) an aliphatic hydrocarbon group which may have a substituent (s), or (10) an optionally protected thiol group; n represents 0 or an integer of 1 to 8; provided that n represents an integer of not less than 2, plural R1 are the same or different; a salt thereof, a solvate thereof or a prodrug thereof has a kinase (especially c-Jun N-terminal kinase) inhibitory activity and an inhibitory activity of a function of AP-1 as a transcription factor, it is useful as a preventive and / or therapeutic agent for a for example, a diabetes of metabolic disease, etc., a rheumatoid arthritis of inflammatory, etc.

The present invention is intended to provide a compound or a pharmacologically acceptable salt thereof which is useful in the treatment of a tumor through its ROS1 kinase enzyme activity inhibitory effect and NTRK kinase enzyme inhibitory effect. The present invention provides a compound having an imidazo[1,2-b]pyridazine structure represented by the general formula (I) or a pharmacologically acceptable salt thereof, and a pharmaceutical composition comprising the compound. In the formula, R1, G, T, Y1, Y2, Y3, and Y4 are as defined herein.

Provided is a uracil compound or a salt thereof, which has potent human dUTPase inhibitory activity and is useful as, for example, an antitumor drug.A uracil compound represented by the general formula (I) or a salt thereof:wherein n represents an integer of 1 to 3; X represents a bond, an oxygen atom, a sulfur atom, or the like; Y represents a linear or branched alkylene group having 1 to 8 carbon atoms, or the like; and Z represents —SO2NR1R2 or —NR3SO2—R4, wherein R1 and R2 each represent an alkyl group having 1 to 6 carbon atoms, an aralkyl group which is optionally substituted, or the like; R3 represents an alkyl group having 1 to 6 carbon atoms, or the like; and R4 represents an aromatic hydrocarbon group, an unsaturated heterocyclic group, or the like.

Provided is a uracil compound or a salt thereof, which has potent human dUTPase inhibitory activity and is useful as, for example, an antitumor drug.A uracil compound represented by the general formula (I) or a salt thereof:wherein n represents an integer of 1 to 3; X represents a bond, an oxygen atom, a sulfur atom, or the like; Y represents a linear or branched alkylene group having 1 to 8 carbon atoms, or the like; and Z represents —SO2NR1R2 or —NR3SO2—R4, wherein R1 and R2 each represent an alkyl group having 1 to 6 carbon atoms, an aralkyl group which is optionally substituted, or the like; R3 represents an alkyl group having 1 to 6 carbon atoms, or the like; and R4 represents an aromatic hydrocarbon group, an unsaturated heterocyclic group, or the like.

The present invention provides a triazolopyridine compound having a prolyl hydroxylase inhibitory action and an erythropoietin production-inducing ability. The present invention relates to a compound represented by the following formula [I]:wherein each symbol is as defined in the specification, or a pharmaceutically acceptable salt thereof, or a solvate thereof, as well as a prolyl hydroxylase inhibitor or erythropoietin production-inducing agent containing the compound. The compound of the present invention shows a prolyl hydroxylase inhibitory action and an erythropoietin production-inducing ability and is useful as a prophylactic or therapeutic agent for various diseases and pathologies (disorders) caused by decreased production of erythropoietin.

The invention provides a deuterium-substituted polycyclic pyridone compound, a prodrug thereof, a composition containing the compound and application of the composition. The deuterium-substituted polycyclic pyridone compound is the compound shown in the formula (I) or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvent compound thereof. The compound and the composition show the cap-dependent endonuclease inhibitory activity and have superior pharmacokinetic properties.

The present invention discloses a method of using biological enzyme decomposition to prepare a hydrolysis compound containing peptide of angiotensin transfer enzyme inhibitory activity, and three novel peptides of high ACE inhibitory activity. For the hydrolysis compound containing peptide of angiotensin transfer enzyme inhibitory activity of the present invention, the oxhide rich in praline is used as the raw material; the product of ACE inhibitory activity IC50 equal to 0.168mg / m can be prepared through the compounding and hydrolysis of biological enzyme. After ultrafiltration, the IC50 is equal to 0.079mg / ml. The means of analysis and detection determines the peptides, ISVPGPM, LGPVGNPGPA and DLSFLPQPPQQ, containing high ACE inhibitory activity. The three peptide sections are novel peptide sections containing high ACE inhibitory activity. Therefore, the three peptides have potential function of lowering blood pressure. The compounding and decomposition of biological enzyme of oxhide is a peptide type hydrolysis product, has inhibitory effects on angiotensin transfer enzyme (ACE), and can be widely used for health food, functional food, auxiliary drugs for lowering blood pressure and other products; the peptide has broad market prospects.

There are disclosed topical compositions for alleviation of skin irritation symptoms or conditions having at least one plant extract effective to inhibit COX-2 enzyme, NGF protein, and / or TNF-alpha protein activity. Preferably, the compositions have a cosmetically, dermatologically, or pharmaceutically acceptable vehicle. In addition to the enzyme inhibitory plant material and acceptable vehicle, compositions may also have at least one active ingredient known to produce skin irritation. There is also a method for treatment of skin irritation symptoms or conditions involving topically applying compositions of the invention. Also disclosed are compositions and methods for topical administration of compositions to the skin that improve the aesthetic appearance of skin and / or provide an anti-aging benefit to the skin.

The present invention provides a commercially applicable method for producing an intermediate of a substituted polycyclic pyridone derivative exhibiting cap-dependent endonuclease inhibitory activity.In the production method shown in the reaction formula (in the formula, the symbols are as defined in the description), by means of an intramolecular cyclisation reaction in which the stereochemistryof a compound shown in formula (III) or formula (VI) is controlled, a compound shown in formula (IV) and including an eliminable functional group on an asymmetric carbon is obtained, and said eliminable functional group is eliminated, whereby an optically active substituted 3-ring pyridone derivative shown in formula (VII) is highly enantioselectively obtained in a high yield.

The invention belongs to the field of medicinal chemistry, and discloses a pyrimidine and triazole containing compound and a preparation method and application thereof in preparation of anti-cancer medicine with lysine specific demethylase 1 (LSD1) being a target. The general formula of the compound is shown in the drawing I. In-vitro LSD1 enzyme inhibition activity experiments prove that by inhibiting LSD1 activity, the compound has obvious inhibiting and killing effects on kinds of cancer cells and can be applied to preparation of the anti-cancer medicine as a further developed lead compound.

Disclosed are novel compounds which are useful as therapeutics, especially in anti-neoplastic therapy and in other therapeutic regimes where cysteine protease inhibition is implicated.

The invention provides a novel herbal composition containing the extracts of the leaves and / or stem of <italic>Argemone mexicana < / highlight>plant, optionally containing the extracts of the fruits of <italic>Cuminum cyminum< / highlight>, which exhibits useful in vitro, in vivo and interesting immunological and pharmacological activities; a process for preparation thereof; and a method of treatment of psoriasis and related immunological and biological disorders by administration of the said novel herbal composition. The useful in vitro, in vivo and interesting immunological and pharmacological activities exhibited by the extracts and fractions of the leaves and / or stem of <italic>Argemone mexicana < / highlight>plant include immunosuppression, lymphoproliferation inhibition, cytokine modulation such as IL-2 inhibition, IFNgamma inhibition, IL-10 induction, keratinocyte proliferation inhibition, keratolytic activity, endothelial cell proliferation inhibition, inhibition of cell adhesion molecule expression such as ICAM-1, MEST inhibition, and enzymes inhibition such as p60src Tyrosine kinase, which are known to be involved in anti-psoriatic activity. The novel herbal composition(s) is useful in the treatment of various disorders, such as psoriasis including plaque psoriasis, gutatte psoriasis, pustular psoriasis and psoriasis of the nails; dermatitis and scleroderma; eczema; inflammatory disorders and other autoimmune diseases like psoriatic arthritis, rheumatoid arthritis, Crohn's disease, multiple sclerosis, irritable bowel disease, ankylosing spondilitis, systemic lupus erythremetosus and Sjogren's syndrome; allergies like asthma and chronic obstructive pulmonary disease and is safe, well-tolerated, non-toxic, with minimal and reversible adverse reactions or side effects, and most importantly, with minimal relapse or recurrence of the disease following completion of a treatment regimen. The invention also describes the presence of phosphodiesterase (III, IV and V) inhibition and 5-Lipoxygenase inhibition in the aqueous, ethanolic or aqueous-ethanolic extracts of fruits of <italic>Cuminum cyminum < / highlight>plant.

The present invention includes multifunctional compositions, methods and binding systems to provide disinfecting and deodorizing coatings for hard and soft surfaces, inorganic and organic solid surfaces and particulate media and other related substrates, including human and animal skin and skin lesions; to provide neutralizing functions for malodors generated by both human, animal and industrial fluids and solid wastes; and to provide neutralizing and degrading functions for nuisance and noxious chemicals. The present invention provides compositions and methods for producing disinfecting, oxidizing and enzyme-inhibiting fluids enabling preparation of durable, stable biocidal and deodorizing coatings and media which can be widely used for biological agent control, prevention and elimination of odors, and degradation of noxious agents susceptible to chemical oxidation, and which take forms that are inoffensive to users and offer high convenience.

The invention relates to an aldose reductase inhibitor for treating chromic complications of diabetes mellitus after being taken orally. The composition comprises natural medicines with aldose reductase inhibition action and at least one medicine with alpha-glycosidase inhibition action and has double actions containing aldose reductase inhibition action and alpha-glycosidase inhibition action. Accidental clinical and pharmacological discovery proves that the composition has the effect of reducing postprandial blood sugar by glycosidase inhibition action and is capable of protecting the retina of a patient with diabetes mellitus, delaying the progress of diabetes mellitus caused senile dementia, and relieving the symptoms of the diabetes mellitus caused senile dementia by virtue of aldose reductase inhibition action.

The invention discloses an angiotensin-converting enzyme inhibitory peptide, and a preparation method and an application thereof, wherein the amino acid sequence of the inhibitory peptide is Leu-Ala-Ser-Pro-Thr-Met. The angiotensin-converting enzyme inhibitory peptide is prepared by tracking, screening and estimating an active ingredient for inhibiting the angiotensin-converting enzyme in mactra veneriformis by virtue of modern biochemical technical means, and purifying the active ingredient by methods of enzymolysis, ultrafiltration, reversed-phase high-performance liquid chromatography and the like; and experiment results indicate that the inhibitory peptide has an excellent effect of inhibiting the angiotensin-converting enzyme and a good anti-hypertension effect, and is good in safety performance, and thus has a bright application prospect.

An oral-applied self-emulsifying polypeptide medicine is prepared from polypeptide, gel adhesive, surfactant, co-surfactant, oil enzyme inhibitor, and diluent. Its preparing process is also disclosed. It features that after it comes in intestinal tract, it is emulsified by itself to become nano-class microemulsion, which can penetrate through intestinal mucosa and epithelial barrier into lymph and blood, and be attached on intestinal inner surface to promote its absorption.

A compound represented by the following general formula (I) or a pharmacologically acceptable salt thereof, wherein R1 represents a C1 to C6 alkyl group which may be substituted by one to three groups selected from substituent group A, or the like (substituent group A: a hydroxy group, a halogeno group, a cyano group, a nitro group, an amino group, a carboxy group, a C1 to C3 alkyl group, etc.); R2, R3, and R8 each independently represent a hydrogen atom or a C1 to C3 alkyl group; R4, R5, R6, R7, R9, and R10 each independently represent a hydrogen atom or the like; and R11 represents a hydrogen atom or the like, has TAFIa enzyme inhibitory activity and is useful as a therapeutic drug for myocardial infarction, angina pectoris, acute coronary syndrome, cerebral infarction, deep vein thrombosis, pulmonary embolism, or the like.

The invention discloses a quinoxalinone derivative with matrix metalloproteinase inhibitory activity and a preparation method and an application thereof, belonging to the technical field of pharmaceutical chemistry. The derivative has the structure shown in the general formula (I), wherein the meanings of R1, R2, R3, R4, R5 and R6 are shown in the patent specification. The compound of the invention is proven to have specific MMP-2 inhibitory activity in the in vitro enzyme inhibitory activity experiments and to be an effective matrix metalloproteinase inhibitor so that the quinoxalinone derivative is expected to be developed to be a new anti-cancer drug.

The invention belongs to the field of medicinal chemistry, and discloses a class of pyrimidotriazole compounds, a preparation method thereof and the use of lysine-specific demethylase (hereinafter referred to as LSD1) as a target in the preparation of antitumor drugs Applications. The general formula of the compound of the present invention is shown in I. The LSD1 enzyme inhibitory activity experiment in vitro proves that this type of compound has obvious inhibitory and killing effects on a variety of tumor cells by inhibiting the activity of LSD1, and can be used as a lead compound for further development and applied to the preparation of anti-tumor drugs.

According to this invention, there is provided an indole derivative having the general formula (I) wherein A is an oxygen atom or a nitrogen atom which nitrogen atom is optionally substituted with an alkyl group, and (i) R<1 >and R<2 >each stand for a hydrogen atom or an alkyl group, independently, or (ii) R<1 >and R<2 >as taken together form a cycloalkyl group or an aromatic ring, or (iii) R<1 >and R<2 >as taken together form a heterocyclic ring, and R<3 >is a hydrogen atom, a (C1-C10)alkyl group or others, R<4 >is a substituted alkyl group and R<5 >is a hydrogen atom, a halogen atom, an alkyl group or an alkoxy group and so on, as novel compounds by a novel chemical synthetic process. The indole derivative of formula (I) exhibits a useful chymase inhibitory activity.

The present invention is intended to provide a compound or a pharmacologically acceptable salt thereof which is useful in the treatment of a tumor through its ROS1 kinase enzyme activity inhibitory effect and NTRK kinase enzyme inhibitory effect. The present invention provides a compound having an imidazo[1,2-b]pyridazine structure represented by the general formula (I) or a pharmacologically acceptable salt thereof, and a pharmaceutical composition comprising the compound. In the formula, R1, G, T, Y1, Y2, Y3, and Y4 are as defined herein.

The invention relates to an acetamides compound and application thereof, and discloses an N-(4-substituted phenyl ethyl) amides compound with a novel structure. An in vitro activity test experiment proves that the compound has the enzyme inhibitory activity on cysteine proteinase (FP-2) and dihydrofolate reductase (DHFR); a malaria-killing experiment result proves that the compound has an inhibition effect on wild and drug-resistant malaria protozoon.

Disclosed relates to a novel chalcone derivative, pharmaceutically acceptable salt thereof, a method for preparing the same and uses thereof, the chalcone derivative being readily obtained through the steps of: reacting aminoacetophenone with sulfonylchloride under the presence of an appropriate salt; and reacting the compound prepared in the above step with hydroxybenzaldehide under the presence of an appropriate catalyst. The chalcone derivative of formula 1 in accordance with the present invention having strong enzyme inhibitory activities for glycosidase can be effectively used in preventing and treating various diseases induced by glycosidase, and the chalcone derivative of the invention having tyrosinase and melanin synthesis inhibitory activities can be effectively used as a skin-whitening compound.

The invention particularly relates to a xanthine oxidase inhibitory peptide. The amino acid sequence of the xanthine oxidase inhibitory peptide is Glu-Glu-Ala-Lys (EEAK). The IC50 value of the tetrapeptide EEAK on xanthine oxidase inhibitory activity is 173.00+ / -0.06 [mu]M, the tetrapeptide EEAK has a continuous and stable inhibitory effect on xanthine oxidase, and the tetrapeptide EEAK has the outstanding advantages of safety, no toxic or side effect, easiness in absorption, industrialization and the like. The active tetrapeptide EEAK or the derivative thereof can be used for preparing gout treatment / prevention medicines or used as a functional food additive for long-term treatment and health care of gout patients, and has a wide application prospect and very important significance.

Disclosed are novel compounds which are useful as therapeutics, especially in anti-neoplastic therapy and in other therapeutic regimes where cysteine protease inhibition is implicated.

The invention discloses a method for screening a triglyceride enzyme inhibitor from a plant extract. The method comprises the following steps of: performing enzyme immobilization by utilizing an adsorption carrier; performing affinity selective separation by utilizing the adsorption carrier loaded with an enzyme to obtain an active compound from the plant extract. According to the method disclosed by the invention, a hollow fiber is used as the adsorption carrier, and a traditional active screening mode of screening after separating is improved into a novel active screening mode of separating after screening and identifying, and thereby, the blindness of compound preparation and separation is greatly reduced. The method can be popularized to be applied to rapidly screen compounds with triglyceride enzyme inhibitory activity in natural products or traditional Chinese medicine mixtures.

The invention relates to a tyrosine kinase inhibitor and a preparation method and use thereof, and belongs to the technical field of pharmaceutical chemistry. The tyrosine kinase inhibitor having the structural features shown in the general formula I, or its pharmaceutically acceptable salts or stereoisomers can effectively inhibit tyrosine kinase activity, and can inhibit kinases such as DDR1, DDR2, Abl, Src, Btk and Kit. Compared with a positive contrast dasatinib, the tyrosine kinase inhibitor has higher half inhibitory concentration or the same half inhibitory concentration, and especially, aiming at DDR1, DDR2, Src, Btk and Kit, the compound 8j has lower K562 cell half inhibitory concentration. The tyrosine kinase inhibitor has good enzyme inhibitory activity and cell activity and has a large application prospect.

Provided is a compound having a D-amino acid oxidase (DAAO) inhibitory action, and useful as, for example, a prophylaxis and / or therapeutic agent for schizophrenia or neuropathic pain.The present inventors have studied a compound that inhibits DAAO, and confirm that a dihydroxy aromatic heterocyclic compound has a DAAO inhibitory action, and completed the present invention. That is, the dihydroxy aromatic heterocyclic compound of the present invention has a good DAAO inhibitory action, and can be used as a prophylaxis and / or therapeutic agent for, for example, schizophrenia or neuropathic pain.