154 results about "Metabolic stability" patented technology

The present invention provides pyrazole-containing fused ring compounds, a pharmaceutical composition thereof and the use thereof. The present invention provides compounds as shown in formula I or pharmaceutically acceptable salts thereof. The compounds are small molecule compounds for non-invasive administration, have the same or similar effect as polypeptide GLP-1 agonists, and have the advantages of one or more of higher biological activity, better metabolic stability and excellent bioavailability.

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 relates to an effective amount of novel benzamide derivative as shown in a general formula (I), a preparation method thereof and application of a pharmaceutical composition containing the derivative as a medicine, compared with the prior art, the compound has better metabolic stability, can be orally taken and has a wider application prospect. # imgabs0 #

The invention belongs to the field of medicines, relates to a heterocyclic compound of a bifunctional chimera for targeted degradation of an androgen receptor and application of the heterocyclic compound, and particularly provides a compound as shown in a formula (I), or a stereoisomer, a tautomer, a nitrogen oxide, a hydrate, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug of the compound, and their use in the treatment of diseases associated with androgen receptors. The compound provided by the invention can degrade androgen receptors in prostate cancer cells in a targeted manner and inhibit proliferation of the prostate cancer cells, and also shows good metabolic stability and pharmacokinetic properties. # imgabs0 #

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.

Disclosed in the present invention are a compound containing (1,3,4-thiadiazole)benzene-1,2-ethylenediamine, a preparation method therefor and a use thereof. The compound has a structural formula. According to the present invention, upon experimental verification, the compound demonstrates potent ferroptosis inhibitory activity and good metabolic stability, and is suitable for the treatment of ferroptosis-related diseases; and the structure can be used as a probe for specific ferroptosis and has two forms of an oxidation state and a reduction state, the probe exhibits green fluorescence in the reduction state, and exhibits blue fluorescence in the oxidation state, and the fluorescence change of the probe can be used as an indicator of the degree of action of an antioxidant, and can be used for detecting the progress of ferroptosis in a sample to be tested, especially for high-sensitivity detection of ONOO-.

The application belongs to the field of chemical drugs, and discloses a BTK protein degrading agent with a silicon-containing group as a hydrophobic tag, a preparation method, a pharmaceutical composition and application thereof.The structure of the BTK protein degrading agent with the silicon-containing group as the hydrophobic tag is shown in formula I, the linker is a saturated aliphatic chain, an unsaturated aliphatic chain, a connecting structure composed of an aromatic ring and a saturated aliphatic chain, or a connecting structure composed of an aromatic ring and an unsaturated aliphatic chain; and R is a specific silicon-containing group as the hydrophobic tag.A BTK protein degrading agent with a silicon-containing group as a hydrophobic tag is obtained, the preparation process is simple and easy to implement, the obtained BTK protein degrading agent has high liver microsomal metabolic stability, has considerable oral bioavailability, shows high treatment efficiency in in-vivo experiments, has a certain inhibitory effect on the proliferation of various tumor cells, and is suitable for the development of cancer drugs such as leukemia.

The present invention provides a formylpiperidine compound, a preparation method and an application thereof. The general structural formula of the formylpiperidine compound is shown in formula (I), or its isomer, or its pharmaceutically acceptable salt, ester or prodrug. The formylpiperidine compound described in the present invention is a dual-target inhibitor of 5-HT reuptake and 5-HT 1A receptor, which can overcome the problems of low clinical efficacy, poor metabolic stability and poor safety of existing antidepressant drugs, and is a compound with a novel structure, high efficiency, stability and low toxicity and having an antidepressant effect.

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 present invention provides novel benzimidazole compounds that act as GLP-1 receptor agonists, as well as methods for preparing such compounds and methods for administering such compounds to mammals in need thereof. The compounds of the present invention exhibit strong GLP-1 receptor agonist effects and good metabolic stability, and have strong specificity for the GLP-1 receptor and pharmaceutical 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.

The invention discloses a cyclo-icaritin carbamate prodrug and salt thereof, belongs to the technical field of medicines, and particularly relates to a carbamate prodrug formed between cyclo-icaritin and amino acid, pharmaceutically acceptable salt of the carbamate prodrug and preparation and application of the carbamate prodrug. Specifically, in combination with the structural characteristics of cycloicaritin and the inherent advantages of the prodrug, amino acid is taken as a modification group and is covalently bound with 3-site hydroxyl in the cycloicaritin structure to form a series of cycloicaritin carbamate prodrugs. According to the compound, the water solubility, permeability and metabolic stability of cycloicaritin can be remarkably improved, the bioavailability of drugs is improved, and the anti-tumor effect is better achieved. # imgabs0 #

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 invention relates to a compound capable of being used as a BET / p300 bromodomain double-target inhibitor or a derivative thereof as well as a preparation method and application of the compound. The compound has a structure as shown in a formula I, wherein substituent groups R1 to R4 in the formula # imgabs0 are defined in the specification. The invention also relates to a pharmaceutical composition containing the compound or the derivative thereof, application of the compound or the derivative thereof as a BET / p300 bromodomain double-target inhibitor, and a preparation method of the compound or the derivative thereof. The compound or the derivative thereof can significantly inhibit the activity of BET / p300 bromodomain, has a significant anti-proliferation effect on cancer cells and multiple myeloma cells, and also has good metabolic stability, safety and drug-likeness, so that the compound or the derivative thereof has a wide application prospect.

The application belongs to the field of chemical drugs, and discloses a PD-L1 protein degrading agent with a silicon-containing group as a hydrophobic tag, a preparation method, a pharmaceutical composition and application thereof. The structure of the PD-L1 protein degrading agent with the silicon-containing group as the hydrophobic tag is shown in formula I, the linker is a saturated aliphatic chain, an unsaturated aliphatic chain, a connecting structure composed of an aromatic ring and a saturated aliphatic chain, or a connecting structure composed of an aromatic ring and an unsaturated aliphatic chain; and R is a specific silicon-containing group as the hydrophobic tag. The application obtains the PD-L1 protein degrading agent with the silicon-containing group as the hydrophobic tag, the preparation process is simple and easy to implement, the obtained PD-L1 protein degrading agent has high liver microsomal metabolic stability, has considerable oral bioavailability, shows high treatment efficiency in in-vivo experiments, has certain inhibition effect on the proliferation of various tumor cells, and is suitable for the development of cancer drugs such as leukemia.

The invention discloses a pyrrole biphenyl derivative compound as well as a preparation method and application thereof in pharmacy, and belongs to the technical field of chemical medicine raw material medicine and preparation manufacturing. The compound has a structure as shown in # imgabs0 #. The compound is specifically combined with SGLT-2 protein through a pyrrole-benzene conjugated system, the glucose transport function of the SGLT-2 protein is inhibited, and the IC50 value of the SGLT-2 protein reaches 15-105 nM. The traditional Chinese medicine composition is suitable for preparing medicines for treating non-alcoholic liver diseases, solid tumors, hematological malignant tumors and autoimmune diseases, and especially has a remarkable effect on abnormal glycolipid metabolism of liver cells and energy deprivation of tumor cells. The compound has deuterated group enhanced metabolic stability, and can be prepared into dosage forms such as tablets, capsules, injection and the like.

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.

Certain triazole compounds have good LPAR1 antagonistic activity and selectivity, low toxicity, and good metabolic stability, and can be used for preventing or treating the LPAR1-related disease or disorder. The IC50 value of some triazole compounds can be below 300 nM, even 50 nM. The range of CC50 of the triazole compounds can be greater than 200 μM. They also show good metabolic stability in human, fancy rats, and house mice.

The invention discloses a tetrazole compound as well as a pharmaceutical composition and application thereof. The invention specifically discloses a compound I, a pharmaceutically acceptable salt thereof, a solvate thereof or a solvate of the salt thereof. The compound I, the pharmaceutically acceptable salt thereof, the solvate thereof or the solvate of the salt thereof have one or more advantages as follows: the structure is novel, the metabolic stability is good, the bioavailability is high, and pulmonary fibrosis pathological injury is effectively relieved. # imgabs0 #