17 results about "Liver microsomes" patented technology

This invention discloses a compound of formula I, or a pharmaceutically acceptable salt, stereoisomer, ester, prodrug, or solvate thereof. Experimental results show that the compound provided by this invention exhibits high inhibitory activity against PAK4 kinase and PAK I / II selectivity, good liver microsomal stability, and rat PK pharmacokinetic properties, especially with low hERG cardiotoxicity risk, representing a significant improvement over prior art compounds.

The invention discloses a bicyclic gamma-amino acid esterified derivative and application thereof, the bicyclic gamma-amino acid esterified derivative can be used as a pain treatment drug through verification, can change a metabolic pathway and accelerate metabolism of liver microsome, so that the burden on the kidney is reduced, and therefore, the bicyclic gamma-amino acid esterified derivative as the pain treatment drug is more widely applicable to people.

This invention belongs to the field of drug metabolism and analytical chemistry, specifically relating to a method for the rapid determination of tigustastat and its active metabolite GD-MET-1 concentrations in a human liver microsome incubation system using liquid chromatography-tandem mass spectrometry (LC-MS / MS). The method first prepares stock solutions of tigustastat, GD-MET-1, and an internal standard, and prepares a series of standard curve solutions, quality control solutions, and precipitant solutions containing the internal standard. Next, the sample with the added precipitant solution undergoes vortexing and centrifugation pretreatment. Finally, chromatographic and mass spectrometric conditions are set, and the analysis is performed by LC-MS / MS. This method has been validated for specificity, accuracy, precision, matrix effects, recovery, residues, and stability, and can be reliably used for metabolic stability studies of tigustastat and GD-MET-1 in a human liver microsome incubation system, GD-MET-1 formation studies, metabolic enzyme identification, enzyme kinetic studies, and drug interaction studies.

The invention discloses a tricyclic compound and application thereof, and belongs to the technical field of medicine synthesis. The invention provides a tricyclic compound as shown in a formula I. The tricyclic compound can be used for broad-spectrum virus resistance, can effectively inhibit the activity of SARS-CoV, MERS-CoV, SARS-CoV-2 and other coronaviruses and block the replication of the viruses in the body of a patient, and particularly has more advantages in the aspects of pharmacokinetic property, human CYP inhibition rate, cytotoxicity, human liver microsome stability and the like. The compound disclosed by the invention can be used as a generic coronavirus resisting drug, and particularly provides a new choice for developing a drug for preventing and treating diseases related to novel coronavirus infection. Formula I

This invention belongs to the field of medicinal chemistry, specifically relating to a dimeric compound with endothelin A (ETA) receptor antagonist activity and its applications. The compound of this invention is rapidly metabolized to atrasentan in human liver microsomes. In rats, after oral administration, it exhibits excellent absorption, high bioavailability, and a long half-life, significantly lowering blood pressure and improving kidney injury. Furthermore, its weak binding to P-GP and its non-substrate nature further enhance its bioavailability. The compound of this invention, or its pharmaceutically acceptable salt, holds promise for use in the preparation of drugs for the treatment and prevention of ETA receptor antagonist-related diseases, such as chronic kidney disease and hypertension.

The present application relates to the technical field of medicine, in particular to a MK-4 analogue, a preparation method and application thereof. The MK-4 analogue provided by the present application is more stable in liver microsomes and has a longer half-life. In the osteogenic experiment of osteoblasts, the osteogenic ability is stronger, which is of great significance for enhancing the specificity, effectiveness and reducing the side effects of drugs, and thus can be used for preparing drugs for preventing and / or treating osteoporosis. As the MK-4 analogue, it is expected to be used for preparing drugs for treating cardiovascular and cerebrovascular diseases, chronic kidney disease, neurodegenerative diseases, diabetes and cancer, etc.

The invention provides a parasite expelling composition and application thereof in yak breeding, the parasite expelling composition comprises albendazole and myrobalan acid, through the synergistic effect of albendazole and myrobalan acid, on one hand, the myrobalan acid inhibits the activity of liver microsome metabolic enzymes, prolongs the half-life period of albendazole, improves the bioavailability and optimizes the pharmacokinetic process, on the other hand, the myrobalan acid inhibits the activity of liver microsome metabolic enzymes, and on the other hand, the myrobalan acid inhibits the activity of liver microsome metabolic enzymes; on the other hand, the two act on parasite tubulin synthesis and a body surface biofilm structure respectively to form double-target synergistic killing, so that the parasite expelling effect is remarkably improved; chebulinic acid can repair gastrointestinal mucosa, regulate flora balance, enhance appetite and effectively counteract irritant injury of albendazole to gastrointestinal tracts; the parasite expelling rate reaches 95% or above, the average daily gain reaches 369 g / d, and no obvious influence is caused to the blood system and liver and kidney functions of yaks; the composition has the characteristics of simple formula, gastrointestinal protection and convenience in administration, is adaptive to the current breeding situation of high parasite infection rate of yaks in plateau pasturing areas, and has a good industrial application prospect.

The invention provides a benzoheterocycle compound, a pharmaceutical composition containing the benzoheterocycle compound and application of the benzoheterocycle compound, and particularly relates to a compound shown in the following formula I, pharmaceutically acceptable salt, stereoisomer, deuterated compound, solvate, prodrug or metabolite of the benzoheterocycle compound, a pharmaceutical composition containing the benzoheterocycle compound and application of the benzoheterocycle compound. The compound disclosed by the invention is a WRN regulating agent with a novel structure, has strong WRN inhibitory activity and MSI HCT116 cell proliferation inhibitory activity, shows excellent selectivity in anti-proliferation activity evaluation of MSI cells HCT116 and MSS cells SW620, shows relatively good stability in in-vitro human liver microsome, has better druggability, and can be applied to preparation of anti-proliferative drugs of human liver microsome, such as liver microsome anti-proliferative drugs, liver microsome anti-proliferative drugs, liver microsome anti-proliferative drugs, liver microsome anti-proliferative drugs, liver microsome anti-proliferative drugs and liver microsome anti-proliferative drugs. The compound can be used as a WRN regulating agent for preparing medicines for preventing or treating diseases related to WRN.

The application discloses a triazolopyridine bromodomain-containing protein 4 (BRD4) small molecule inhibitor and a preparation method and application thereof, a compound or a pharmaceutically acceptable salt or a racemate thereof, the general formula of which is shown as formula (I). The novel synthetic triazolopyridine compound effectively regulates the occurrence and development process of related diseases by inhibiting the activity of BRD4 protein. In addition to the advantage of inhibiting the activity of BRD4 protein, the compound has good water solubility and liver microsomal stability, which means that it can be better absorbed and distributed in the body, thereby improving the therapeutic effect. The compound also has good drugability, so that it can be better applied to various inflammatory, autoimmune diseases and tumor drugs. The application provides a new choice for the treatment of related diseases and is expected to play an important role in clinical practice.

The invention belongs to the field of anti-infection drugs, and discloses a protease inhibitor for treating or preventing virus infection and application thereof. The protease inhibitor is a compound represented by the following formula (I) and pharmaceutically acceptable salts, esters, prodrugs, solvates and isomers thereof: the compound is a novel protease inhibitor, can inhibit proteins encoded by coronavirus or interfere with the life cycle of the coronavirus, and can also be used as an antiviral agent, such as an anti-inflammatory agent, an anti-inflammatory agent and an anti-inflammatory agent. The 3CL protease inhibitor is used for treating respiratory system diseases, and compared with the prior art, the 3CL protease inhibitor provided by the invention is high in activity, lower in cytotoxicity, high in metabolic stability in liver microsomes, higher in bioavailability, better in drug absorption, distribution, metabolism and excretion properties, free of inhibition on main CYP enzymes and lower in DDI risk.

The application belongs to the field of chemical drugs, and discloses a protein degrading agent taking noradamantane as a hydrophobic group, a preparation method, a pharmaceutical composition and application thereof. The application provides a protein degrading agent capable of degrading AR, which is based on noradamantane with a hydrophobic tag function as a hydrophobic group and an enzalutamide parent core as a target protein ligand. The protein degrading agent prepared by the application can effectively induce degradation of AR and AR-V7 in a cancer cell line. Compared with the AR protein degrading agent based on adamantane as a hydrophobic tag reported by the previous person, the protein degrading agent has considerable improvement in liver microsomal metabolic stability, can exhibit excellent in-vivo anti-prostate cancer effect in low-frequency drug administration, can be applied to preparation of an AR degrading agent, can form a pharmaceutical composition, and is suitable for development of a cancer drug such as a prostate cancer drug.

The invention discloses a macrocyclic compound as well as an intermediate, a preparation method and application thereof. Specifically provided is a compound represented by formula (I) or a pharmaceutically acceptable salt thereof. The compound provided by the invention has one or more of the following effects and advantages: (1) the compound has good inhibitory activity on KRAS G12C mutation; (2) the compound has good inhibitory activity on KRAS G12V mutation; (3) the compound has good inhibitory activity on KRAS G12D mutation; (4) the half-life period is long; (5) the oral bioavailability is high; (6) the stability of the liver microsome is good; (7) the target tissue distribution is high; and (8) the pharmaceutical composition has good pharmacokinetic characteristics and druggability.

The present application provides a kind of compound as PAK4 inhibitor, with the structure shown in formula I or its tautomer, meso, racemate, enantiomer, diastereoisomer or its mixture form, pharmaceutically acceptable hydrate, solvate or salt.The test results show that the compound prepared by the present application has high inhibitory activity and selectivity for PAK4 kinase, and its liver microsomal stability and rat PK have also been improved to a certain extent.

The invention discloses an N-pyridine piperazine compound as well as a preparation method and application thereof, and belongs to the technical field of chemical pharmacy. The structure of the imidazopyridine compound is as shown in formula I: (I), R is-OH,-H,-OR1 or-NHR2, and R1 and R2 are respectively and independently selected from hydrogen, C1-C6 alkyl, C1-C8 cycloalkyl, aryl, substituted aryl, heteroaryl and substituted heteroaryl. The novel N-pyridine piperazine compound prepared by the invention is simple and feasible in preparation process, and pharmacological experiments find that the N-pyridine piperazine compound provided by the invention shows USP5 enzymatic inhibitory activity and inhibitory activity to various tumor cells, is more sensitive to breast cancer cells, and can be used for preparing the novel N-pyridine piperazine compound. The compound has good plasma stability, liver microsome metabolism stability and oral bioavailability, shows efficient anti-breast cancer activity in vivo and in vitro, and is suitable for development of anti-breast cancer drugs.

Disclosed are a deuterated 1,4-benzodiazepine-2,5-dione compound and the use thereof. Provided is a compound as represented by formula I or a pharmaceutically acceptable salt thereof. The disclosed 1,4-benzodiazepine-2,5-dione active compound maintains the activity of inhibiting tumor cells and tumor stem cells, and prolongs the degradation function of in-vitro human liver microsomes on the compound, such that the half-life period is significantly prolonged, which provides a safer and more reliable candidate for developing new anti-tumor drugs.

The invention provides a mixed polycyclic aromatic hydrocarbon cell co-culture system model as well as a construction method and application thereof, and belongs to the technical field of cell models. The mixed PAHs cell co-culture system model is obtained by performing corresponding PAHs stimulation on peripheral blood mononuclear lymphocytes cultured in vitro by referring to the variety and concentration of PAHs in bodies of healthy people, and the model can comprehensively reflect the comprehensive influence of PAHs caused by atmospheric pollution on organisms; according to the model, the PAHs mix is pre-activated by using liver microsomes, so that the action effect of the PAHs in a human body is well simulated. The mixed PAHs cell co-culture system model can be used for evaluating the comprehensive influence of mixed PAHs on human cells and the drug treatment effect, and has a wide application prospect.

The application discloses a kind of FGFR inhibitors and preparation method, pharmaceutical composition and application thereof.The compound structure is as shown in formula I, also includes stereoisomer, pharmaceutically acceptable salt or their mixture thereof.The FGFR inhibitor and the pharmaceutical composition thereof have high efficient inhibiting effect on wild type and mutant FGFR, can be used to prepare the drug of FGFR related disease, the prepared drug can exert pharmacodynamic effect at molecular level and cell level, is widely applied, and has excellent liver microsomal stability, long half-life in vivo, high bioavailability, with good drug-like properties.In addition, the synthesis method of the compound is simple and easy to operate.