206 results about "Metabolic stability" patented technology

Compounds represented by general formula (I) (all of the symbols in the formula conform to the definitions in the Description) are compounds that, in addition to having a Btk-selective inhibitory activity, exhibit an excellent metabolic stability and can avoid hepatotoxicity or the like, and as a consequence can provide safe therapeutic agents for diseases in which B cells or mast cells participate.

Compounds represented by general formula (I) (all of the symbols in the formula conform to the definitions in the Description) are compounds that, in addition to having a Btk-selective inhibitory activity, exhibit an excellent metabolic stability and can avoid hepatotoxicity or the like, and as a consequence can provide safe therapeutic agents for diseases in which B cells or mast cells participate.

The purinone derivative 6-amino-9-[(3R)-1-(2-butynoyl)-3-pyrrolidinyl]-7-(4-phenoxyphenyl)-7,9-dihydro-8H-purin-8-one hydrochloride has Btk-selective inhibitory activity and, in addition to having excellent metabolic stability, it is a compound that exhibits a high level of solubility and absorption with respect to the free base and can be crystallized, hence it can serve as a therapeutic agent for diseases involving B cells and mast cells.

Human receptor selective atrial natriuretic factor variants containing various substitutions, especially G16R, show equal potency and binding affinity for the human A-receptor but have decreased affinity for the human clearance or C-receptor. These ANF variants have natriuretic, diuretic and vasorelaxant activity but have increased metabolic stability, making them suitable for treating congestive heart failure, acute kidney failure and renal hypertension.

The invention discloses a method for preparing a block polymer micelle freeze-drying preparation carrying docetaxel, which uses a PEO-PPO-PEO block polymer as a micelle carrier to wrap the docetaxel inside the micelle and comprises the following steps: (1) dissolving the carrier and the docetaxel into an organic solvent to make the PEO-PPO-PEO block polymer and the docetaxel fully dissolved in the organic solvent, and then preparing aqueous solution of the docetaxel micelle by using the PEO-PPO-PEO block polymer as the carrier; and (2) adding a freeze-drying protective agent into the aqueous solution of the PEO-PPO-PEO block polymer carrying micelle, and filtering, sterilizing and freeze-drying the mixture to obtain freeze-drying preparation of the carrier micelle system. The block polymer micelle freeze-drying preparation carrying the docetaxel can increase the dissolubility, metabolic stability and in vivo circulation time of the docetaxel, reduce the toxicity and improve the bioavailability, and is more suitable for clinical application.

Provided is an ORL-1 receptor agonist having improved bioavailability based on superior metabolic stability and strong and high selectivity, as compared to conventional compounds. A compound represented by the formula (I) wherein each symbol is as defined in the claims.

The present invention provides an antifungal agent that has excellent antifungal action, and is also excellent in terms of its properties, safety, and metabolic stability. The present invention discloses a compound represented by the following formula I or a salt thereof, and an antifungal agent comprising the compound or the salt:wherein R1 represents a hydrogen atom, a halogen atom, an amino group, a C1-6 alkyl group, a C1-6 alkoxy group, or a C1-6-alkoxy-C1-6-alkyl group; R2 represents a hydrogen atom or an amino group; X, Y, Z, and W independently represent a nitrogen atom, an oxygen atom, a sulfur atom, or —CH—, provided that at least two among X, Y, and W are nitrogen atoms; the ring A represents a 5- or 6-membered heteroaryl ring or a benzene ring; Q represents a methylene group, an oxygen atom, —CH2O—, —OCH2—, —NH—, —NHCH2—, or —CH2NH—; and R3 represents a C1-6 alkyl group, a C3-8 cycloalkyl group, a C6-10 aryl group, or a 5- or 6-membered heteroaryl group, each of which may have one or two substituents.

The invention is directed to analogs of LHRH-II and, more generally, to analogs of the LHRH family in which modifications have been made that confer enhanced binding affinity for LHRH receptors and / or improved metabolic stability.The invention is further directed to methods of targeted therapy and targeted imaging in patients with sex-hormone-related cancers or other LHRH-mediated diseases.

The present invention provides an antifungal agent that has superior antifungal action and is also superior in terms of physical properties, safety and metabolic stability. The present invention discloses a compound represented by the formula (I):(wherein X represents an oxygen atom, a sulfur atom or —NH—, R1 represents a hydrogen atom, a halogen atom, a cyano group, an amino group or a substituent, and R2 and R3 independently represent a hydrogen atom, a halogen atom, a hydroxyl group or a substituent, except for a case in which R2 and R3 are both hydrogen atoms), and an antifungal agent containing the above compound.

The invention discloses a nitrile methyl piperazine derivative serving as a KRAS G12C mutant protein inhibitor and an application of the nitrile methyl piperazine derivative. The compound has a structure represented by a general formula (I). Compared with an existing compound, the compound provided by the invention has higher selectivity on malignant tumors caused by KRAS G12C mutation; a longer half-life period is shown, and better metabolic stability is achieved; the exposure amount is higher, the oral bioavailability is better, and the anti-tumor activity is more remarkable.

The invention provides an antiviral nucleoside phosphoramidate and a pharmaceutical composition and applications thereof. The nucleoside phosphoramidate compound is prepared by connecting nucleoside with phosphate through phosphorus-oxygen bonds. The structural formulas of the nucleoside phosphoramidate compound are represented by a, a1, a2, b, b1, and b2. The invention also discloses stereoisomers, pharmaceutically acceptable salts, hydrates, solvates, or crystals of the nucleoside phosphoramidate compound. The anti-hepatitis C activity of the provided novel nucleoside phosphoramidate is obviously better than that of sofosbuvir used in clinic. On the saccharide ring, the fluorine atoms are replaced by chlorine atoms, and the cytotoxicity of measure cell lines is prominently reduced. By systematically modifying and optimizing the basic groups, saccharide rings, and prodrugs, the anti-hepatitis C activity of partial synthesized compounds is 2 to 10 times higher than that of sofosbuvir. At the same time, the key parts of metabolism are optimized, the metabolism stability and chemical stability of synthesized compounds in plasma are better, compared with those of sofosbuvir.

The invention discloses nitrogen-containing heterocyclic ring compounds, and a preparation method, pharmaceutical compositions and application thereof. The nitrogen-containing heterocyclic ring compounds as shown in a formula II which is described in the specification can effectively bind to the bromodomains of BRD4, BRD3, BRD2 and BRDT in the BET family so as to regulate the transcription of thedownstream gene c-myc and related target genes thereof, thereby regulating downstream signal pathways and playing specific roles, including treatment of diseases such as inflammatory diseases, cancersand AIDS; and a part of the compounds have high activity, and good cell activity and metabolic stability, and thus can be used as effective drugs for treating tumors.

The present invention provides an antifungal agent that has superior antifungal action and is also superior in terms of physical properties, safety and metabolic stability. The present invention discloses a compound represented by the formula (I):(wherein X represents an oxygen atom, a sulfur atom or —NH—, R1 represents a hydrogen atom, a halogen atom, a cyano group, an amino group or a substituent, and R2 and R3 independently represent a hydrogen atom, a halogen atom, a hydroxyl group or a substituent, except for a case in which R2 and R3 are both hydrogen atoms), and an antifungal agent containing the above compound.

The invention relates to a 2-amino-1-(4-nitrobenzophenone)-1-ethanol metalloproteinase inhibitor as well as a preparation and application thereof. The 2-amino-1-(4-nitrobenzophenone)-1-ethanol metalloproteinase inhibitor is a compound with the following general formula (1). Dipeptide-like or kyrine-type compounds of different series can enhance the appetency and metabolization stability of a compound and an enzyme or a receptor and conforms to the basic requirement on inhibitor structures. The invention designs and synthesizes a group of aminopeptidase N inhibitors with totally new structures. A vitro test shows that the inhibitors have no cytotoxin activity, and four compounds which exhibit remarkable vitro inhibitory activity are close to positive control medicine bestatin and can be used as candidate anticancer medicines. The invention also relates to a pharmaceutical composition of a peptide-like compound with a structure indicated by formula (I), and also relates to the pharmacy usage of the pharmaceutical composition.

The invention discloses a heterocyclic compound, an intermediate, and a preparation method and application thereof. The invention provides a heterocyclic compound shown as a formula I, and a stereoisomer, a geometrical isomer, a tautomer or a pharmaceutically acceptable salt thereof. The heterocyclic compound has high P2X3 antagonistic activity, good selectivity, low toxicity, good metabolic stability and small influence on taste.

Methods are disclosed for developing models used to rapidly predict metabolic stability and regioselectivity of drug molecules. Training sets, based on a sample of molecules with known reaction rates and / or activation energies, are used along with structural descriptors of the molecules in order to develop mathematical models of metabolism based on regression analysis of the activation energies and descriptors. The resulting models are then used to predict the metabolism of other molecules. The invention is particularly useful in developing simple models of cytochrome p450 enzyme metabolism.

The invention discloses compounds or optical isomers, pharmaceutically acceptable salts, hydrates or solvates of the compounds. The compounds are represented by a formula (I), wherein R<1> to R<18> are each independently selected from hydrogen and deuterium, and not all hydrogen. The compounds, the salts, the hydrates or the solvates of the compounds provided by the invention can be used as a FAKinhibitor and used for preparing an anticancer drug, and compared with undeuterated control compound Defactinib, the compounds provided by the invention have significantly-improved metabolism stability and pharmacokinetic performance, and have excellent application prospects.

The invention discloses nitrogen-containing heterocyclic ring compounds, and a preparation method, pharmaceutical compositions and application thereof. The nitrogen-containing heterocyclic ring compounds as shown in a formula II which is described in the specification can effectively bind to the bromodomains of BRD4, BRD3, BRD2 and BRDT in the BET family so as to regulate the transcription of thedownstream gene c-myc and related target genes thereof, thereby regulating downstream signal pathways and playing specific roles, including treatment of diseases such as inflammatory diseases, cancersand AIDS; and a part of the compounds have high activity, and good cell activity and metabolic stability, and thus can be used as effective drugs for treating tumors.

The present invention discloses a compound represented by formula (I), or an optical isomer, a pharmaceutically acceptable salt, a prodrug, a hydrate or a solvate thereof. In the formula (I), R1-R10 are respectively and independently selected from H, D, and are not all H. Compared with a non-deuterated control compound MGL3196, the compound or the optical isomer, the pharmaceutically acceptable salt, the prodrug, the hydrate or the solvate of the compound provided by the invention have the advantages that the agonistic activity on thyroid hormone receptor beta (THR-beta) is better; half-life period is longer, clearance rate is higher, metabolic stability and pharmacokinetic properties are better, and the application prospect in preparation method of THR-beta agonists, and medicines used for treating THR-beta agonist adaptation diseases including dyslipidemia, hypercholesterolemia, non-alcoholic steatohepatitis (NASH) and non-alcoholic fatty liver disease (NAFLD) is promising.

The invention discloses a spiral ring or bridged ring containing pyrimidine compound. The compound has a structure shown as formula I, and also can be an enantiomer, a diastereomer, a pharmaceutically acceptable salt, a prodrug molecule, a solvate, a tautomer, a resonant body and an isotope marker of formula I. Through the way, the spiral ring or bridged ring containing pyrimidine compound can effectively inhibit the growth of various tumor cells, also generates an inhibiting effect on EGFR (epidermal growth factor receptor), and other proteases of Her family, can be used for preparing antitumor drugs, and also can overcome the drug resistance induced by gefitinib, erlotinib and other existing drugs. Compared with similar non-spiral ring or bridged ring pyrimidine compounds, the spiral ring or bridged ring containing pyrimidine compound I can better improve the biological metabolic stability.

The invention provides a GLP-1 (glucagon-like peptide-1) analogue modified with PEG (polyethylene glycol). The GLP-1analogue has an amino acid sequence shown in SEQ ID NO: 1-19, and the cysteine residue of the amino acid sequence is modified with a PEG group. The invention further provides an application of the analogue or analogue composition in preparation of drugs for treating diabetes, obesity and Alzheimer's disease. The polypeptide has better metabolism stability, has remarkably prolonged in-vivo half-life period, solves the problem that the half-life period of natural GLP-1 is short, can substantially improve the clinical application compliance and has higher application value.

The invention relates to a substituted pyrazolo [1,5-a] pyrimidine compound used as a Trk kinase inhibitor, or pharmacologically acceptable salt, a medicine composition and a purpose. A pyrazolo [1,5-a] pyrimidine derivative in the structure with a general formula (I) shown as the accompanying drawing has good Trk family protein tyrosine kinase inhibition activity and metabolism stability.

The present invention provides methods and kits for determining the metabolic stability of compounds (e.g., stability to oxidative metabolism). In particular embodiments, the invention provides a method of determining the susceptibility of a compound to metabolism by an enzyme. In one representative embodiment, the enzyme is a cytochrome P450 enzyme. The invention is well-adapted for use in high throughput drug screening programs.

Modifications of the peptide pyrrhocoricin permit the production of a variety of anti-bacterial or anti-fungal peptides having general formula R1-Asp-Lys-Gly-X-Y-Leu-Pro-Arg-Pro-Thr-Pro-Pro-Arg-Pro-Ile-Tyr-X′-Y′-R2 SEQ ID NO: 1 or multimeric compositions containing more than a single peptide of that formula. These peptides may be straight chain or cyclic peptides, and may contain one or more non-cleavable bonds. These peptides are characterized by anti-bacterial or anti-fungal activity and metabolic stability in mammalian serum. These peptides are useful in anti-bacterial or anti-fungal pharmaceutical compositions and for further drug development or identification of other antibiotic or anti-fungal compounds.

The invention relates to a culturing method for body fluid derived tumor cells and a tumor medium. The method comprises the steps of enriching body fluid tumor cells; mixing the body fluid tumor cellswith an extracellular matrix; and in the presence of a basic medium, adding corresponding pleural effusion, ascites or cerebrospinal fluid and the like to carry out 3D cell culture. By the method, apatient derived tumor analog (PDTA) can be obtained effectively, and a novel detecting tool is provided for detection of sensitivity of clinical tumor patients to drugs and measurement of in-vitro metabolic stability, metabolic profiling, toxicity and the like of drug candidates.

Novel diagnostic and therapeutic peptides disclosed herein are somatostatin analogs backbone cyclized through metal complexation, and having improved somatostatin receptor subtype affinity and selectivity. These backbone cyclized peptide analogs possess unique and superior properties over other analogs, including chemical and metabolic stability, selectivity, increased bioavailability and improved pharmacokinetics. Pharmaceutical compositions that include these backbone cyclized somatostatin analogs, radiolabelled analogs, reagents for synthesizing same, and methods of using such compositions for diagnostic and therapeutic purposes are also disclosed.

The present invention discloses a stabilized cell-penetrating peptide with a hydrophobic side chain and a preparation method and use of the stabilized cell-penetrating peptide. The stabilized cell-penetrating peptide comprises a cell-penetrating peptidyl peptide and the hydrophobic side chain, and the cell-penetrating peptidyl peptide is a cell-penetrating peptide rich in arginine; and the hydrophobic side chain contains hydrophobic small molecules, the stabilized cell-penetrating peptide is a cyclic peptide with a cyclized side chain and obtained by introducing two natural cysteines into a sequence of the cell-penetrating peptidyl peptide and crosslinking the cell-penetrating peptidyl peptide with the hydrophobic small molecules by an alkylation / arylation reaction of the cysteines. The preparation method of the stabilized cell-penetrating peptide is simple and effective, besides, metabolic stability and cell-penetrating capacity of the cell-penetrating peptide are remarkably improvedby adjusting conformation of the amino acids and hydrophilicity and hydrophobicity of the side chain, deep penetration of in-vitro cell spheres and living tumor tissues by the cell-penetrating peptideis realized, and the cell-penetrating peptide has a good application prospect in the field of medicine delivery.

The invention provides 2, 3, 5, 7-tetrasubstituted dihydro-pyrazolo piperidine derivative and a preparation method and application thereof. The derivative is 2, 3-bis(substituted phenyl)-5-subsituted arylmethyl-7-substituted benzylidene dihydro-pyrazolo piperidine derivative, having the following formula (I). The preparation method includes using substituted arylmethyl amine and methyl acrylate as raw materials; subjecting the materials to Michael addition, Dieckmann condensation and hydrolysis-decarboxylation sequentially; allowing for Aldol reaction with substituted benzaldehyde to obtain intermediate N-substituted arylmethyl-3, 5-bis(substituted benzylidene)-4-piperidone; allowing for condensation with substituted phenylhydrazine to obtain a compound according to the formula (I). The derivative is efficient in inhibiting multiplication of various carcinoma cell lines such as leukemia, esophagus cancer, ovarian cancer and breast cancer in human, is well stably metabolic in liver microsomes of human and rat, is free of direct and competitive inhibition on five enzymes of liver microsomes, such as CYP3A4, CYP2D6, CYP2C9, CYP1A2 and CYP2C19, is highly bioavailable, is low in toxicity to normal cells, and is available for the preparation of drugs for the cancers.

The invention relates to the technical field of biology, in particular to dendrobium officinale and a dendrobium officinale extract combined probiotics for regulating blood sugar and blood fat, and improving diabetes and metabolic syndrome and alleviating occurrence of related complications so as to maintain metabolic stability of organisms. The dendrobium officinale has the effects of regulatingand controlling blood sugar, enhancing body immunity and the like; the probiotics is an active microorganism beneficial to a host, can regulate intestinal flora balance, and can generate an exact health effect so as to improve the micro-ecological balance of the host and play a beneficial role. According to the invention, the dendrobium officinale exerts the effects of reducing blood sugar and blood fat, prebiotics can promote the growth of probiotics and regulate glucose uptake and improve the gastrointestinal irritation caused by taking the probiotics alone, so that the probiotics and dendrobium officinale can better play the role in reducing blood sugar, complications are reduced, and a pharmaceutical composition for preventing or treating diabetes mellitus and metabolic syndromes can be prepared by the probiotics and dendrobium officinale. Therefore, the product provides a new application for improving diabetes and metabolic syndrome related diseases.