13results about How to "High metabolic stability" patented technology

The present invention belongs to the field of bioengineering technology, and specifically relates to a human growth hormone fusion protein and its application. The fusion protein hGH-linker-HSA and the hGH mutant fusion protein hGHmutF31Q / V90E-linker-HSA are constructed by connecting hGH and HSA through a connecting peptide. Mouse experiments show that hGHmutF31Q / V90E-linker-HSA can improve the metabolic stability of hGH, prolong the half-life of hGH, and enhance the administration effect of hGH, and has a broad application prospect in clinical practice.

The application of the invention relates to an atorvastatin calcium derivative and a preparation method thereof, the developed novel atorvastatin derivative realizes multiple optimization through molecular design: fluorine atoms are introduced at para-positions of aromatic rings, and the metabolic stability is improved by utilizing high bond energy of C-F bonds and strong electronegativity of the fluorine atoms; a phosphate group is introduced, so that the oral bioavailability is improved by 30-40%. The synergistic effect of fluorine atoms and phosphate groups optimizes the combination with HMG-CoA reductase, and the combination energy is improved by about 15%. Through structural modification, the logP value is reduced from 5.7 to 4.5, and the water solubility is improved. The new derivative not only improves the enzyme inhibition activity by 20-30%, but also can bring additional treatment advantages through multi-target action, and provides a better treatment choice for patients with hyperlipidemia.

The invention relates to the technical field of metabonomics analysis, in particular to application of a metabolic marker in preparation of a head and neck squamous cell carcinoma diagnostic product, a kit, a screening method of the metabolic marker of the head and neck squamous cell carcinoma, a diagnostic model and a construction method and application of the diagnostic model. The metabolic marker comprises at least one of lactic acid, sphingosine, cadaverine, uridine diphosphate, allantoic acid, hydroxyproline, sphingosine-1-phosphoric acid, indole-3-acetaldehyde, pantothenic acid, fumaric acid, malic acid, prostaglandin or ornithine in red blood cells and / or plasma. The screened red blood cells and plasma metabolism markers can be used for predicting or diagnosing the head and neck squamous cell carcinoma respectively or independently, particularly, the red blood cell metabolism markers can provide more stable tumor microenvironment information, and the metabolism stability is high and is not easily influenced by diet and circadian rhythm.

This invention discloses a highly efficient oxygen removal reagent and its application in the deoxygenation reconstruction of carbon resource molecular skeletons, comprising a pivot reagent, a phosphine reagent, an azo reagent, a reducing agent, an acid reagent, a base reagent, a photosensitizer, and an organic solvent; wherein, X in the pivot reagent includes a hydrazine group or a sulfone group; PG is a protecting group; LG is a leaving group; by using natural oxygen-containing functional groups such as alcohols, aldehydes, and ketones as direct coupling precursors, an integrated in-situ activation-deoxygenation coupling process is achieved, significantly reducing reaction steps.

The present application relates to the technical field of biological medicine, in particular to a gemcitabine-indoleamine 2,3-dioxygenase inhibitor conjugate, a prodrug nanomicelle, a preparation method and an application. The conjugate covalently connects gemcitabine and NLG919 through a connecting arm containing a triazole structure, forms an amphiphilic molecule with a hydrophilic-hydrophobic structure, and can self-assemble into stable small-size nanomicelles in an aqueous solution. The nanomicelle has a pH and enzyme dual-responsive drug release property, can improve the stability and delivery efficiency of gemcitabine, promote cell uptake, and enhance the synergistic antitumor effect of chemotherapy and immunomodulation. The present application also provides an application of the nanomicelle in the preparation of an antitumor drug.

The invention belongs to the technical field of heterocyclic compounds, and particularly relates to a Kv7 potassium ion channel opener as well as a preparation method and application thereof. The method comprises the following steps: adding a compound 1, a compound 2 and triethylamine into ethyl acetate, and carrying out a first reaction to obtain a reaction solution; performing extraction, water washing, drying and vacuum concentration on the reaction liquid, and then adding the reaction liquid into a mixed solution of a sodium hydroxide aqueous solution and isopropanol to perform a second reaction to obtain a compound 3; adding the compound 3, a catalyst and NH4HCO2 into the mixed solvent, and carrying out amination reaction to obtain a compound 4; and adding the compound 4, the compound 5 and triethylamine into ethyl acetate for reaction to obtain the Kv7 potassium ion channel opener. The metabolic stability and the structural rigidity are improved.

The invention discloses a tanshinone IIA derivative as well as a preparation method and application thereof, and provides a set of systematic chemical synthesis route for overcoming the defects that tanshinone IIA is poor in water solubility and low in bioavailability and the antitumor activity needs to be improved. A series of novel derivatives with various structures and general formula structures and pharmaceutical salts thereof are prepared. The core of the technical scheme is that after a specific functional group is introduced into the derivative, the water solubility and the stability of the compound are remarkably improved, and the derivative particularly shows excellent anti-colorectal cancer activity, can effectively inhibit tumor cell proliferation and tumor growth in an animal model, and does not have obvious toxic or side effects. The invention also provides a pharmaceutical composition containing the derivative and application of the pharmaceutical composition in preparation of medicines for preventing, relieving or treating colorectal cancer, and provides an important candidate compound for developing a high-efficiency and low-toxicity novel anti-colorectal cancer medicine.

The invention discloses an application of a compound in preparation of a medicine for treating allergic rhinitis. The CDK2 inhibitor can relieve inflammatory infiltration of nasal mucosa tissues, effectively improve the inflammatory degree of allergic rhinitis and reduce secretion of mucus, and has a remarkable curative effect on treating allergic rhinitis. The raw materials involved in the designed synthesis route are easy to obtain, the reaction operation is simple, the reaction condition is mild, the method can be used for industrial production, and the obtained medicine has wide application and transformation and great practical value.

The invention relates to the technical field of paclitaxel, and particularly discloses difluoromethylated paclitaxel and a preparation method thereof. The invention relates to difluoromethylated paclitaxel. The difluoromethylated paclitaxel comprises direct difluoromethylated paclitaxel and deoxidized difluoromethylated paclitaxel. The difluoromethylated paclitaxel provided by the invention can be used in clinical drugs, and has the advantages of improved drug utilization rate, high selectivity, high target cell pertinence and the like. In addition, the preparation method has the advantages of mild reaction conditions, high yield, wide substrate applicability and the like.

The invention discloses an N-methyl nitrosamide compound as well as a pharmaceutical composition and application thereof. The compound (formula I) is a hypoxia-activated NO donor drug, has the characteristic of effectively releasing NO under a high-selectivity hypoxia condition, so that the activity of myocardial cells is remarkably improved, the in-vivo and in-vitro activity is excellent, and the compound can be used for preventing or treating myocardial hypoxia injury. Meanwhile, the metabolic stability of the compound is improved by an ether bond connection structure, so that the compound has in-vivo metabolic properties beneficial to patent medicines.

The invention discloses a curcumin glycosyl derivative as well as a preparation method and medical application thereof. The structure of the curcumin glycosyl derivative is shown in the specification. According to the invention, D-glucose is utilized to modify a drug through ester bond connection, then the drug is targeted to GLUT1, and the drug is transferred to penetrate through a blood brain barrier to reach brain tissues, so that the targeting property of the drug is remarkably improved. In addition, through F atom modification, the bond energy and reactivity of F atoms are lower than those of H atoms, the molecular weight of F atoms is smaller than that of other closed groups, and the influence on the molecular size is small. The compound can block sites which are prone to oxidative metabolism, so that the metabolic stability of the compound is improved, and the action time of the medicine in vivo is prolonged. # imgabs0 #

The invention discloses a method for preparing carbon isotope labeled levodopa through asymmetric synthesis. The method comprises the following steps: carrying out nucleophilic addition reaction on carbon isotope labeled CO2 and an aryl nucleophilic reagent to obtain carbon isotope labeled pepper acid; carrying out reduction and bromination reaction on piperic acid to synthesize a carbon isotope labeled aryl bromide fragment; the aryl bromide fragment and a chiral auxiliary Schiff base fragment are connected through an asymmetric alkylation reaction, and the carbon isotope labeled levodopa is obtained by removing an auxiliary and a protecting group from a connection product. According to the method, cheap and easily available raw materials are adopted, the cost is low, the yield is high, and the chiral center stereo enantioselectivity is high; according to the method, the L-DOPA can be accurately and stably labeled at the levodopa 3 site at a fixed point, the metabolic stability of the carbon isotope labeled L-DOPA is improved, the asymmetric synthesis of the carbon isotope labeled L-DOPA at the levodopa 3 site is completed for the first time, and a material support is provided for metabolism research related to the levodopa.

The invention provides a 5 '-modified 2', 5 '-connected nucleotide monomer and an application of the 5'-modified 2 ', 5'-connected nucleotide monomer at a siRNA antisense strand 5 '-terminal. The 5 '-modified nucleotide monomer provided by the invention is an unconventional 2', 5 '-connected nucleotide monomer. The oligonucleotide carrying the 5 '-modified 2', 5 '-connected nucleotide monomer is a double-stranded siRNA molecule, the 5'-modified 2 ', 5'-connected nucleotide monomer is introduced to the 1 # site of the 5 '-terminal of an antisense strand of the siRNA, so that the siRNA can silence a target gene mRNA with higher efficiency and longer timeliness, and the oligonucleotide can be used for treating related diseases caused by the target gene mRNA.