63results about How to "Dose-dependent improvement" patented technology

The invention relates to 4-cycloaminoalkoxy-3-methoxycinnamates, and a preparation method and application thereof. The preparation method is characterized by comprising the following steps: 1. preparing ferulic acid acyl chlorides from the initial raw material ferulic acid under the conditions of a first solvent and an acylating agent; 2. carrying out reaction on the ferulic acid acyl chlorides and alcohol or phenol in a second solvent under the first alkaline condition to obtain corresponding ferulates; and 3. carrying out reaction on the ferulates and 1-substituted-4-chloroalkylpiperidine in a third solvent under the second alkaline condition to generate the 4-cycloaminoalkoxy-3-methoxycinnamates. The compounds have favorable effects on treating and/or preventing neurodegeneration related diseases, including but not limited to vascular dementia, Alzheimer's disease, Parkinson's disease, Huntington's disease, HIV (human immunodeficiency virus) related dementia, multilocular sclerosis, progressive lateral spinal sclerosis, neuropathic pains, glaucoma and the like.

The invention belongs to the technical field of organic synthesis and particularly relates to a cyclamine alkylamide ferulate compound as well as a preparation method and application thereof. The preparation method comprises the following steps: enabling potassium phthalimide serving as a start raw material to react with 1-substituted-4-haloalkyl piperidine under the effects of a solvent and alkali to obtain a phthalimide alkylamine compound; performing hydrazinolysis of the phthalimide alkylamine compound and hydrazine hydrate to obtain a primary amine compound; and adding ferulic acid, a condensing agent and a solvent into the primary amine compound for a condensation reaction to obtain a product of cyclamine alkylamide ferulate compound. The cyclamine alkylamide ferulate compound provided by the invention is of a simple chemical structure, the chemical reactions in the preparation process are thorough, the product yield is high, the operation is convenient, the cost is low, and the product can be used for perfectly treating the neurodegenerative diseases.

The invention successfully screens a virus strain VR18 suitable for building an animal model of CA16 infection and builds the animal model of the CA16 virus infection by infecting a suckling mouse with the virus strain VR18. The invention also relates to a method for building the animal model of the CA16 injection and the use of the virus stain VR18 in the building of the animal model of the CA16infection and the like. The method provides valuable experiment data for study on CA16 vaccines.

The invention relates to 4-amino alkoxy-3-methoxy cinnamic acid benzamide compounds as well as preparation methods and applications thereof. The preparation methods of the compounds comprise the following steps: step 1, ferulic acid is taken as a starting material and subjected to a reaction with substituted aniline under the conditions of a first solvent and a condensing agent, and corresponding ferulic acid benzamide compounds are obtained; step 2, the ferulic acid benzamide compounds are subjected to a reaction with a dihalogenated alkyl compound under the condition of a second solvent and a first alkaline condition, and a corresponding halogen compounds are obtained; step 3, the halogen compounds are subjected to a reaction with an organic amine compound under the condition of a third solvent, and the 4-amino alkoxy-3-methoxy cinnamic acid benzamide compounds are obtained. The compounds have a remarkable inhibiting effect on acetylcholinesterase, the IC50 is 0.01 mu M-5 mu M, and the inhibitory activity on acetylcholinesterase is greatly higher than that on butyrylcholinesterase, so that the compounds have certain selective inhibiting effect on acetylcholinesterase.

The invention relates to a 4-cyclamine alkoxy-3-methoxyl cinnamic acid benzamide compound, a preparation method and application of the compound.The chemical structure general formula of the compound is shown as a formula (I) (please see the formula in the description), wherein m represents 1-12, R1 represents C1-C12 alkyl or benzyl or substituted benzyl, X represents C1-C12 alkyl or benzyl or substituted benzyl, phenyl of which a benzene ring is substituted with 1-4 groups selected from F, Cl, Br, I, C(1-4) alkyl, C(1-4) alkoxy, trifluoromethyl, trifluoromethoxy, nitryl, a cyano group, and the substituent groups can be located at any position of the benzene ring.Accordingly, the compound has the significant inhibiting effect on acetylcholinesterase, the IC50 of the compound is 0.01-5 micromoles per liter, the inhibiting activity on acetylcholinesterase is greatly higher than the inhibiting activity on butyrylcholine esterase, and therefore the compound has the certain selective inhibiting effect on acetylcholinesterase.

An application of schisandrin A in treating the drug-resistant tumor is disclosed. It can be used in conjunction with antineoplastic for increasing the sensitivity of tumor to antineoplastic.

The invention discloses triptolide and application of composition of triptolide to preparation of medicine for resisting esophageal cancer. A research proves that the triptolide has an obvious inhibition effect on proliferation of human esophageal cancer cells, represents the obvious dose dependence and has the prospect that the triptolide is developed and prepared into the medicine for resistingthe esophageal cancer. The triptolide and natural compound erianin having the effect of resisting the esophageal cancer also have the effect of cooperatively inhibiting the proliferation of the humanesophageal cancer cells, and therefore, the triptolide and the erianin can be prepared into a medicine composition for chemotherapy of the human esophageal cancer.

The invention relates to application of 3,15-dicarbonyl gibberellic acid methyl ester (GA) in reversing tumor multidrug resistance. A compound GA provided in the invention has favorable activity on the reversing tumor multidrug resistance (MDR), the GA acting on K562/A02 has higher drug susceptibility and can obviously reverse the drug resistance of the K562/A02 for ADM (Archer Daniels Midland); the effect mechanism of the GA for reversing the multidrug resistance of K562/A02 cells is realized by increasing the contents of chemotherapeutic drugs in the drug-resistance cells to prevent the chemotherapeutic drugs from being discharged outwards and promote the apoptosis of the drug-resistance cells, and has no obvious relevance with the expression of down-regulated drug-resistance genes mdr-1, thereby prompting that the action mechanism of the GA is relevant to the outward discharging pump function of inhibiting the drug-resistance cells P-gp and inducing the apoptosis of the drug-resistance cells; and the compound GA has lower toxicity, and therefore the compound GA has favorable application prospect on clinical tumor chemotherapy and particularly on resisting clinical tumor drug resistance.

The invention provides an application of notoginseng saponins Rg 1 in preparing medicine for treating pulmonary interstitial fibrosis. Pharmacological experiments show that if in vitro, the notoginseng saponins Rg 1 can inhibit the activity of human embryonic lung fibroblast and has good dose-dependent; if in vivo, the notoginseng saponins Rg 1 can decrease the lung coefficientand the lung hydroxyproline content of a mouse with pulmonary interstitial fibrosis; the notoginseng saponins Rg 1 can also reduce the pulmonary alveolitis and the degree of pulmonary interstitial fibrosis of the mouse with pulmonary interstitial fibrosis; the raw materials of the notoginseng saponins Rg 1 are easy to obtain, and can be prepared into various common dosage forms such as tablets, capsules, and injections; and the preparation method is simple.

The invention relates to a 4-amine alkoxy-3-methoxyl cinnamic acid ester compound, a preparation method and application of the compound.The preparation method of the compound comprises the following steps that 1, a ferulic acid acyl chloride compound is obtained by taking ferulic acid as a staring material under the condition of in first solvent under the condition of an acylating agent; 2, the ferulic acid acyl chloride compound reacts with alcohol or phenol in second solvent under a first alkaline condition to obtain a corresponding cinnamic acid ester compound; 3, the cinnamic acid ester compound reacts with a dihalogen alkyl compound in third solvent under a second alkaline condition to generate a corresponding halogen compound; 4, the halogen compound reacts with an organic amine compound in fourth solvent to obtain the 4-amine alkoxy-3-methoxyl cinnamic acid ester compound.Accordingly, the compound has the significant inhibiting effect on acetylcholinesterase, the inhibiting activity on acetylcholinesterase is greatly higher than the inhibiting activity on butyrylcholine esterase, and the certain selective inhibiting effect on acetylcholinesterase is achieved.

The present invention relates to a new pharmaceutical use of fucoidan, ie., prevention and treatment of male reproductive toxicity caused by organophosphorus pesticide, further to applications of the fucoidan in preparation of drugs for inhibition of sperm motility decreasing, abnormal sperm increasing, testis tissue MDA content increasing, testis tissue CAT activity decreasing and testis tissue LDH activity decreasing caused by organophosphorus pesticide. According to the present invention, the high-toxicity organophosphorus pesticide monocrotophos and the low-toxicity organophosphorus pesticide phoxim are adopted as the representatives to research the prevention and treatment effect of the fucoidan on male reproductive toxicity caused by the low-concentration organophosphorus pesticide, such that it is proved that the fucoidan can inhibit the male reproductive toxicity caused by the organophosphorus pesticide, and has a good dose-dependent manner so as to provide the applications of the fucoidan as the active substance in preparation of the drugs for prevention and control of male reproductive toxicity caused by the organophosphorus pesticide.

The invention provides a composite of breviscapinum and panax notoginseng saponins Rg1 for treating pulmonary fibrosis, wherein the weight ratio of the breviscapinum to the panax notoginseng saponins Rg1 is 2-5:1-2. The invention also provides application of the composite in the preparation of a medicament for treating the pulmonary fibrosis. The composite of the breviscapinum and the panax notoginseng saponins Rg1 is formulated in a certain proportion and has the advantages of favorable pulmonary fibrosis resistance, remarkable effect and little side effects. Raw materials of the composite are easily obtained and can be prepared in various common dosage forms, such as tablets, capsules, injections and the like, through a conventional method with simple preparation method. The pharmacological action of the composite is obvious; in vitro, the composite can inhibit the activity of human embryonic lung fibroblasts and has favorable dosage dependence; and in vivo, the composite can lower the lung coefficient of a mouse with the pulmonary fibrosis and the content of hydroxyproline of lung tissues and also relieve the alveolitis of the mouse with the pulmonary fibrosis and reduce the degree of the pulmonary fibrosis.

The invention discloses a cell line method pyrogen detection method and a kit. The method includes following steps: (1) a pyrogen material standard solution and a to-be-detected sample solution is prepared; (2) the pyrogen material standard solution or the to-be-detected sample solution are respectively added into a HL-60 cell-containing cell culture solution for culture, and cultured cell supernatant is taken; and (3) the content of cytokine IL-6 in the cultured cell supernatant of the step (2). According to the method, human body pyrogen reaction can be simulated, Gram-negative bacterium sourced, Gram-positive bacterium sourced and yeast sourced pyrogen materials can be qualitatively and quantitatively analyzed, sensitivity is high, and the method is simple and easy. The kit includes the pyrogen material standard solution, a cytokine IL-6 detection agent and HL-60 cells, the kit has the advantages of simple operation, capability of pyrogen material qualitative and quantitative analysis, and high sensitivity.

The invention relates to 6-(pyridine-4-yl)-4-substituted amino quinazoline and quinoline compounds having PI3K inhibitory activity, which are compounds of formula (I) structure (as shown in the description), or solvates, enantiomers, diastereoisomers, tautomers or any-ratio mixtures of their pharmaceutically acceptable salts, including racemic mixtures. The 6-(pyridine-4-yl)-4-substituted amino quinazoline and quinoline compounds have good inhibitory action against PI3K, show good antitumor effect, and has a good prospect in the preparation of drugs for treatment of diseases responsive to PI3Kalpha and/or PI3K delta. The invention also relates to pharmaceutical application of the compounds as PI3K inhibitors.

The invention discloses biomedical application of ophiobollin to preparation of a Gli gene inhibitor and a liver cancer prevention and treatment drug. The invention discovers that ophiobollin A and Cand 6-epi-ophiobolin N can significantly inhibit the proliferation of liver cancer cells through inhibiting Gli1 and Gli2 gene expression, and the inhibiting effect shows an obvious dosage dependence;the ophiobollin A and C and the 6-epi-ophiobolin N are effective inhibitors for Gli1 and Gli2 genes and can be used for preparing the liver cancer prevention and treatment drug. Technical personnel in the field know that the inhibition of the Gli1 and Gli2 gene expression is a more mature anticancer molecular pathway, and the ophiobollin A and C and the 6-epi-ophiobolin N play an anti-cancer rolethrough the pathway. The prior art does not disclose research results of the invention.