101 results about "Metabolic stability" patented technology

The invention discloses a multi-target joint optimized antibiotic molecule design system and method applied to the field of biological medicine, and the method comprises the steps: obtaining FabI enzyme and AcrAB-TolC efflux pump structure data, extracting double-target space and physicochemical characteristics, and constructing a joint pharmacophore model containing a FabI inhibition domain and an efflux pump blocking domain; screening candidate molecules meeting a double-domain space matching threshold, screening high-affinity double-target molecules through conformation sampling and free energy calculation, and forming a lead compound library through multi-layer filtration of metabolic stability, membrane penetrability, quantum chemical properties and synthesis feasibility; carrying out electron effect, chain length or heteroatom fine tuning on dominant molecules through in-vitro bacteriostasis and efflux inhibition experiment feedback, and carrying out iterative optimization until MIClt is met; 2 [mu] g / mL and the efflux inhibition rate is gt; according to the present invention, the antibacterial effect and the drug resistance inhibition ability are significantly improved, the molecular synthesizability and the biological safety are ensured, and the engineering design new path is provided for the Gram-negative bacterium drug resistance crisis.

The invention belongs to the technical field of microorganisms, and particularly relates to a strain for producing high-optical-purity L-lactic acid and application of the strain. The strain is preserved in the China General Microbiological Culture Collection Center (CGMCC) on May 13, 2025, and the preservation number of the strain is CGMCC No. 34537; the preservation address is Institute of Microbiology, Chinese Academy of Sciences, No.3, Yard 1, Beichen West Road, Chaoyang District, Beijing. When the strain is used for fermentation production of L-lactic acid, the fermentation period is short, the sugar-acid conversion rate is high, the yield of L-lactic acid is high, and the optical purity is high. In addition, the strain also has excellent growth and metabolism stability, lactic acid with optical purity can still be efficiently produced after passage to the tenth generation, and the strain is suitable for industrial production of high-purity L-lactic acid.

The application provides use of a compound A or a pharmaceutically acceptable salt thereof as a Bruton's tyrosine kinase (BTK) inhibitor in preparation of a drug for treating a BTK-related tumor disease. In vitro and in vivo test results show that the compound A has good inhibitory activity on BTK kinase, good inhibitory activity on human B-cell lymphoma cells with high BTK expression, and good in vivo anti-tumor activity. In addition, the compound A has good pharmacokinetic properties and metabolic stability, and can be used for developing a drug preparation for treating a BTK-related tumor disease, and has important clinical application value.

This invention belongs to the field of biomedical technology and provides a polypeptide with ATG8 protein binding activity, comprising the following structure: X1-X2-X3-X4-X5-X6-X7; wherein: X1, X2, and X3 are independently selected from glutamic acid or are absent; X4 is selected from tryptophan, phenylalanine, or leucine; X5 is valine; X6 is selected from leucine, isoleucine, or valine; and X7 is selected from valine, tryptophan, phenylalanine, or tyrosine. Compared with existing autophagy inhibitors, this polypeptide has the following superior pharmacokinetic potential and development flexibility in terms of target selection, binding strength, and mechanism of action: the short sequence not only reduces synthesis costs but also leaves more room for modification, which is expected to significantly improve the metabolic stability and drug-likeness potential of the polypeptide; it can serve as a highly efficient ATG8 targeting ligand and can be widely used in the construction of biochemical probes, screening of PPI competitive inhibitors, and the development of targeted delivery systems.

Provided are an amphotericin B amide derivative and a use thereof. The amphotericin B amide derivative is as shown in formula (I). The compound has good antifungal activity, is effective against various fungi, has good water solubility, is adapted to be developed into an injection dosage form, has excellent metabolic stability in animals (such as mice, rats, dogs, and monkeys), has a long half-life period, can effectively reduce the frequency of administration, has weak inhibition on CYP enzymes, and has a low risk of drug interaction.

The present application relates to arylalkylamine compounds, and preparation methods and uses thereof, the arylalkylamine compounds of the present application have the following formula (I): wherein X, Y are as defined in the specification. The compounds of the present application have excellent CaSR agonistic activity, high bioavailability, high in vivo metabolic stability, and high safety.

The invention discloses an aromatic alkylamine ferroptosis inhibitor based on a butylphthalide structure and a preparation method and application thereof. The chemical structural formula of the ferroptosis inhibitor is shown as a formula 1 or a formula 2. The ferroptosis inhibitor can inhibit ferroptosis caused by a ferroptosis inducer and can reduce the level of active oxygen in cells. Nerve injury caused by cerebral ischemia reperfusion can be relieved, and symptoms of neurological diseases such as Alzheimer's disease and Parkinson's disease can be relieved; compared with a ferroptosis inhibitor Ferrostatin-1, the aryl alkyl amine compound disclosed by the invention has better metabolic stability and is suitable for in-vivo drug effect evaluation. Therefore, the novel aryl alkyl amine compound provided by the invention has a very good application value in treatment of neurological diseases related to ferroptosis.

The invention provides an amphotericin B amide derivative and application thereof. The amphotericin B amide derivative is shown as a formula (I), has good antifungal activity, is effective to various fungi, has good water solubility, is suitable for being developed into injections, has excellent metabolic stability in animal bodies (such as mice, rats, dogs and monkeys), is long in half-life period, can effectively reduce the administration frequency, is weak in CYP enzyme inhibition, and can be used for preparing the antifungal drugs. The drug interaction risk is low.

The present invention provides a cyclic peptide compound optionally linked to a nucleic acid, the cyclic peptide compound having a cyclic moiety wherein: (1) the cyclic moiety is composed of 13 or 14 amino acid residues; (2) among the amino acid residues constituting the cyclic moiety, the number of N-substituted amino acid residues is 7 or more, the number of amino acid residues in a single side chain is 3 or fewer, and the number of native amino acid residues is 4 or fewer; and (3) the ClogP / total amide bond (ClogP / total AB) is 1.0 to 1.8.

This invention relates to the field of natural active ingredient research technology, specifically to the application of walnut peptides in the preparation of cognitive function improvers. The cognitive function improver is a core functional short peptide derived from walnuts, characterized by high bioactivity, non-toxicity, and favorable pharmacokinetic properties. Its amino acid sequence is AFVHWY. This short peptide is easily synthesized artificially and possesses characteristics such as easy oral administration, easy absorption, strong metabolic stability, and strong blood-brain barrier penetration, providing a novel solution for the prevention and improvement of cognitive impairment.

The invention discloses imidazopyridine derivatives and application thereof, a pharmaceutical composition and a pharmaceutical preparation, and belongs to the technical field of medical chemistry. The technical problems to be solved are that the existing P2X3 receptor inhibitor is poor in safety, low in P2X3 or P2X2 / 3 selectivity, poor in metabolic stability and the like. According to the key points of the technical scheme, the imidazopyridine derivative is selected from a compound as shown in a formula I or a racemate, a stereoisomer, a geometric isomer, a tautomer, a nitrogen oxide, a hydrate, an isotope label, a solvate, a polymorphic substance, a metabolite, an ester, a pharmaceutically acceptable salt or a prodrug thereof.

The invention provides a somatostatin receptor targeting compound and application thereof. The compound is a compound as shown in a formula (I), or a stereoisomer, a tautomer, a eutectic, a polymorphic substance, a solvate, an isotope label, a pharmaceutically acceptable salt or a prodrug of the compound as shown in the formula (I). The compound has nano-friction-level high affinity to a somatostatin receptor, can specifically target and express tumor cells of the somatostatin receptor, has good metabolic stability in tumor tissues, can maintain effective concentration for a long time, and is beneficial to continuous, efficient and specific aggregation of drugs at tumor parts.

The application discloses an imidazopyridine derivative and application, a pharmaceutical composition and a pharmaceutical preparation, and belongs to the technical field of medicinal chemistry. The technical problems to be solved are that existing P2X3 receptor inhibitors have poor safety, low selectivity for P2X3 or P2X2 / 3 and poor metabolic stability. The technical solution is that an imidazopyridine derivative is selected from the compounds shown in the formula I or racemates, stereoisomers, geometric isomers, tautomers, nitroxides, hydrates, isotopically labeled compounds, solvates, polymorphs, metabolites, esters, pharmaceutically acceptable salts or prodrugs.

Disclosed are an aromatic alkylamine ferroptosis inhibitor based on a butylphthalide structure, a preparation method therefor, and an application thereof. The chemical structural formula of the ferroptosis inhibitor is as shown in formula (1) or formula (2). The ferroptosis inhibitor is capable of inhibiting ferroptosis caused by a ferroptosis inducer, and reduces the level of intracellular reactive oxygen species. The ferroptosis inhibitor reduces neurological damage caused by cerebral ischemia-reperfusion, and alleviates symptoms of neurological disorders such as Alzheimer's disease and Parkinson's disease. Compared to the ferroptosis inhibitor Ferrostatin-1, the arylalkylamine compound exhibits better metabolic stability and is suitable for in-vivo efficacy evaluation. Therefore, the novel arylalkylamine compound provided by the present invention demonstrates great application value in the treatment of ferroptosis-related neurological disorders.

The present application relates to the field of biotechnology, and more particularly to an inhibitory peptide targeting p53 protein and application thereof. The present application uses IDProMat to design and obtain the inhibitory peptide targeting p53 protein according to the core binding site of the binding interface of the p53 protein core domain and ASPP2, TSPYL5, iASPP and the like; the inhibitory peptide can bind to p53 protein, competitively block the interaction between E3 ubiquitin ligase COP1 and p53, inhibit the ubiquitination degradation of p53, restore the anticancer function of p53, and has good biological safety and metabolic stability, and is expected to be used for clinical treatment of ovarian cancer, cervical cancer, endometrial cancer, pancreatic cancer and the like.

This invention belongs to the field of biomedicine, specifically relating to the development and application of oligonucleotide drugs targeting the key assembly proteins G3BP1 / 2 of stress granules. The oligonucleotides in these drugs are all composed of 20 bases, with 5 bases at each end modified with 2'-O-methoxyethyl, and 10 consecutive ordinary bases in the middle to ensure targeting specificity. Simultaneously, the entire nucleic acid chain is modified with thiophosphorylation. The oligonucleotide molecules disclosed in this invention possess targeting specificity, high molecular activity, and in vivo metabolic stability, providing research directions and candidate drugs for clinical targeting of stress granules and improvement of neurodegenerative diseases such as ALS.

The present invention provides a cyclic peptide compound optionally linked to a nucleic acid, wherein the cyclic peptide compound contains a cyclic portion, (1) the cyclic portion is composed of 13 or 14 amino acid residues, (2) among the amino acid residues composing the cyclic portion, the number of N-substituted amino acid residues is 7 or more, the number of amino acid residues having the same side chain is 3 or less, and the number of natural amino acid residues is 4 or less, and (3) ClogP / total amide bond (ClogP / total AB) is 1.0 to 1.8.

The present application relates to an amide compound and its use, the amide compound is selected from the compound shown in formula (I), its tautomer, its endo racemate, its exo racemate, its enantiomer, its diastereoisomer, its atropisomer or its pharmaceutically acceptable salt. The present application develops a series of novel amide compounds, these amide compounds have excellent anti-HIV virus activity, and no obvious cytotoxicity, strong affinity to HIV-1 capsid protein, good specificity; suitable for intravenous administration, oral administration, subcutaneous administration, intramuscular administration mode, long half-life in vivo and high exposure; at the same time, the amide compound has no obvious inhibition to various CYP enzymes, shows high plasma protein binding, excellent safety and good metabolic stability in vivo, no potential off-target effect, high safety, and has the potential to develop into a clinical long-acting drug.

The invention provides an N-(hydroxyalkyl pyridyl) tetrahydrofuran carboxamide compound, a prodrug, an oxide, a salt, a metal complex or a stereochemical isomer, a pharmaceutical composition containing the N-(hydroxyalkyl pyridyl) tetrahydrofuran carboxamide compound, an application of the N-(hydroxyalkyl pyridyl) tetrahydrofuran carboxamide compound as a Nav inhibitor and an application of the N-(hydroxyalkyl pyridyl) tetrahydrofuran carboxamide compound in preparation of drugs for treating and / or relieving pain and pain related diseases. The compound provided by the invention has the advantages of high metabolic stability, high oral absorption, better bioavailability, better activity, higher selectivity, better pharmacokinetic property, quicker effect, low cardiac side effect and the like.

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.

Disclosed in the present invention are a FAP-targeting compound and a preparation method therefor. By means of a meticulously designed molecular structure containing a plurality of variable substituents, the compound can precisely target fibroblasts in tumor stroma, thereby providing a new approach for cancer treatment. The Z group of the compound can be flexibly replaced by a radioactive agent, fluorescent agent or contrast agent, thus broadens the application range for tumor diagnosis and treatment. In the preparation method, starting from a starting material, a high-purity and high-yield FAP-targeting compound is ultimately obtained via a plurality of efficient reaction steps. Such compound has good metabolic stability and pharmacokinetic properties, which reduce the side effects of medications and increase the therapeutic effect. The diverse substituents and linker arms of the compound further optimize the physicochemical properties and improve the overall therapeutic effect. When combined with a pharmaceutical carrier, the compound achieves efficient delivery to tumor tissues and reduces non-target side effects, which provides a precise and effective personalized treatment regimen for cancer patients, and significantly improves the therapeutic effect and the quality of life of patients.

This invention discloses a pyrrolobenzene derivative compound, its preparation method, and its pharmaceutical application, belonging to the field of chemical pharmaceutical raw materials and formulation manufacturing technology. The compound has the structure shown. This compound specifically binds to the SGLT-2 protein through a pyrrolobenzene conjugated system, inhibiting its glucose transport function and affecting the IC50 of SGLT-2. 50 Values ​​range from 15 to 105 nM. Suitable for preparing drugs to treat non-alcoholic liver disease, solid tumors, hematological malignancies, and autoimmune diseases, especially effective against abnormal glucose and lipid metabolism in hepatocytes and energy deprivation in tumor cells. The compound possesses enhanced metabolic stability due to its deuterated group and can be formulated into tablets, capsules, injections, and other dosage forms.

The invention belongs to the technical field of medicinal chemistry and pharmacology, and discloses a diphyllin amide derivative as well as a preparation method and application thereof. The diphyllin thioether derivative has a structure as shown in the following formula, wherein R represents one of phenyl, 3-fluorophenyl, 2-thienyl, 2-pyrrolyl and tert-butyl. The diphyllin amide derivative disclosed by the invention is a diphyllin amide derivative with a non-glycoside structure, does not contain structures such as glycosidic bonds and double bonds which are easy to hydrolyze in vivo, has the metabolic stability superior to that of glycoside compounds, has relatively strong tumor cell proliferation inhibition activity, and can be applied to preparation of medicines for treating cancers such as liver cancer, colorectal adenocarcinoma and lung cancer.

The invention discloses a novel BimBH3 mimic peptide analogue constructed on the basis of a nailing and fatty acid acylation dual-modification strategy and application of the novel BimBH3 mimic peptide analogue serving as a PTPN1 inhibitor to development of a long-acting hypoglycemic drug. The structural general formula of the BimBH3 mimic peptide analogue is as shown in a formula I. The structural general formula of the BimBH3 mimic peptide analogue is as shown in a formula I. The invention provides the BimBH3 mimic peptide analogue with a novel structure, and the BimBH3 mimic peptide analogue is constructed by adopting a nailing and fatty acid acylation dual-modification strategy and has the structural general formula as shown in the formula I. The invention further provides a preparation method of the BimBH3 mimic peptide analogue. On the basis of a BimBH3 functional domain core sequence, the novel BimBH3 mimic peptide analogue has target inhibitory activity, metabolic stability and in-vivo action durability through second-site lysine substitution, N-terminal palmitic acid conjugation and fifth, sixth and ninth site glutamic acid side chain mediated synthesis ring nailing modification, and the synthesis ring nailing mode is molecular lactam cyclization. Experiments show that the compound can efficiently inhibit PTPN1 activity, has a long-acting hypoglycemic effect in a type 2 diabetes animal model, and has the potential of being developed into a long-acting antidiabetic drug which is administered once a week. The invention also discloses a solid-phase synthesis preparation method of the compound and application of the compound as a potential PTPN1 inhibitor drug.

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 application provides a solid form, a crystalline form, a crystal form of compound A, a solvate or a hydrate thereof, a preparation method and application, the obtained crystalline form of compound A has good crystallinity and stability, compound A has good Bruton tyrosine kinase inhibitory activity, cell inhibitory activity, in-vivo anti-tumor activity, pharmacokinetic properties and metabolic stability.

The present application relates to a kind of targeted degradation androgen receptor bifunctional chimeric heterocyclic compound and its purposes, specifically provides the compound shown in formula (I), or its isotopic compound, or its optical isomer, or its tautomer, or its pharmaceutically acceptable salt, or its prodrug, or its solvate, wherein, ARB is androgen receptor recognition / binding portion, L is linking portion, U is ubiquitin protease recognition / binding portion;Three parts are connected by chemical bond.The above-mentioned compound provided by the present application can target degradation androgen receptor in prostate cancer cell, and inhibit the proliferation of prostate cancer cell, also show good metabolic stability and pharmacokinetic property.The compound of the present application has good application prospect in the preparation of androgen receptor protein degradation targeting chimera, and the preparation of the drug for treating related diseases (including prostate cancer, breast cancer, Kennedy disease) regulated by androgen receptor.

Disclosed is a heterocyclic compound as represented by formula (I), a tautomer thereof, or a pharmaceutically acceptable salt thereof. The compound has better inhibitory activity on TRPC5, has good metabolic stability in liver micro-particles, and has good clinical pharmacokinetic properties.

The invention relates to the field of organic synthesis, and relates to a preparation method of a novel N-polyfluoroalkylamine compound, the compound is represented by a formula I. A is selected from P or S, R1 is selected from any one of F, Cl, N, alkyl, phenyl, alkoxy, alkylthio, phenoxyl, thiophenyl or amido, R2 is selected from any one of F, Cl, N, alkyl, phenyl, alkoxy, alkylthio, phenoxyl, thiophenyl and amido, and R3 is selected from any one of F, Cl, N, alkyl, phenyl, alkyl, alkyl, alkyl, phenyl, alkoxy, alkylthio, phenoxyl, thiophenyl and amido. R < 2 > is selected from any one of O, N, alkyl, phenyl, alkoxy, alkylthio, phenoxyl, thiophenyl or amido, R < 3 > is selected from any one of alkyl, alkenyl, phenyl, naphthyl, ester group, pyridyl, thienyl, indolyl, furyl or pyrrolyl, R < 4 > is CFxH (3-x) or CF2R < 5 >, R < 5 > is selected from one of CF3 or phenoxyl, and x is 2 or 3; according to the invention, a compound containing active fluorine is introduced to a nitrogen atom, so that the metabolic stability and the radioactive labeling capability are improved, and a brand new way is opened up for designing more intelligent drugs and probes.