179 results about "Metabolic stability" patented technology

Provided are deuterated analogs of MDMA, including deuterated empathogens. In some embodiments, such compounds are monoamine releasers or inhibit monoamine transporters. In some aspects, features of the compounds provide stability, such as metabolic stability, and efficacy. Also provided are methods for the preparation of deuterated empathogens and pharmaceutical compositions comprising the same. Methods of using the deuterated empathogens, alone or in combination with other therapeutic agents, are provided. In some embodiments, deuterated empathogens are used to treat CNS disorders, such as mental health conditions and neurodegenerative disorders.

The invention provides an N-(hydroxyalkyl pyridyl) tetrahydrofuran carboxamide compound, a prodrug, an oxide, a salt, a metal complex or a stereochemical isomer of a sodium channel regulator and a pharmaceutical composition containing the N-(hydroxyalkyl pyridyl) tetrahydrofuran carboxamide compound, the prodrug, the oxide, the salt, the metal complex or the stereochemical isomer. And their use as Nav inhibitors and their use in the preparation of medicaments for the treatment and / or alleviation of 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 discloses a BimBH3 analogue containing D-type amino acid and N-terminal fatty acid acylation, a preparation method of the BimBH3 analogue and application of the BimBH3 analogue as a PTPN1 inhibitor to development of hypoglycemic drugs. The structural general formula of the novel BimBH3 mimic peptide analogue is shown as a formula I: # imgabs0 #, wherein Raa2 is equal to D-His, D-Leu, D-Pro, D-Ser, D-Arg, D-Gln, D-Lys, D-Trp, D-Val, D-Tyr, D-Ala, Raa3 is equal to D-Gln, Raa7 is equal to D-Arg, and Raa8 is equal to D-Allo-Ile. The mimic peptide compound is derived from a core region of a Bim-BH3 structural domain, different D-type amino acid site-specific replacement modification and N-terminal conjugated hexadecanoic acid modification are adopted for amino acids at the second, third, seventh and eighth sites respectively, the BimBH3 mimic peptide modified by the D-type amino acid is more stable and has higher metabolic stability, and the target binding capacity and inhibitory activity of the BimBH3 mimic peptide can still be reserved or even improved. The BimBH3 mimic peptide compound shows an excellent PTPN1 inhibitor, the ability of resisting protease hydrolase and various digestive enzymes is also remarkably improved, and the BimBH3 mimic peptide compound has longer pharmacological action time and can play a potential long-acting hypoglycemic role through subcutaneous injection or oral administration. The compound is completely prepared by a polypeptide solid-phase synthesis method, and an obtained crude product is subjected to semi-preparative liquid chromatography purification and freeze-drying to obtain a target compound.

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 #

New synthetic methods to provide access to previously unexplored functionality at the C8 position of substituted imidazo[5,1-d][1,2,3,5]tetrazines of Formula I. Through synthesis and evaluation of a suite of compounds with a range of aqueous stabilities (from 0.5 to 40 hours), a predictive model for imidazotetrazine hydrolytic stability based on the Hammett constant of the C8 substituent was derived. Promising compounds were identified that possess activity against a panel of GBM cell lines, appropriate hydrolytic and metabolic stability, and brain-to-serum ratios dramatically elevated relative to TMZ, leading to lower hematological toxicity profiles and superior activity to TMZ in a mouse model of GBM.

Use of a compound in the treatment of liver diseases. Experimental results show that the compound has a relatively high liver-tissue-targeting property, very low toxicity to liver primary cells and high liver safety, has significant efficacy on liver diseases such as viral hepatitis (e.g., hepatitis B) and liver cancers (including primary liver cancers and metastatic liver cancers), and has relatively good physicochemical properties, metabolic stability, bioavailability and safety, thus having very good drug development prospects.

The invention discloses application of a compound in treatment of liver diseases. Experimental results show that the compound has relatively high liver tissue targeting property, very low toxicity to liver primary cells, high liver safety and obvious curative effects on liver diseases such as viral hepatitis (such as hepatitis B), liver cancer (including primary liver cancer and metastatic liver cancer) and the like; in addition, the compound also has better physicochemical properties, metabolic stability, bioavailability and safety, and has a very good drug development prospect.

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 invention relates to a difunctional chimera heterocyclic compound for targeted degradation of an androgen receptor and application of the difunctional chimera heterocyclic compound, and particularly provides a compound shown in a formula (I), or an isotope compound of the compound, or an optical isomer of the compound, or a tautomer of the compound, or a pharmaceutically acceptable salt of the compound, or a prodrug of the compound, or a solvate of the compound, aRB is an androgen receptor recognition / combination part, L is a linking part, and U is a ubiquitin protease recognition / combination part; the three parts are connected through chemical bonds. 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. The compound provided by the invention has a good application prospect in preparation of a protein degradation targeting chimera of an androgen receptor and in preparation of drugs for treating related diseases (including prostatic cancer, breast cancer and Kenildie disease) regulated and controlled by the androgen receptor. # imgabs0 #

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.

The present invention belongs to the field of bioengineering technology, and specifically relates to a human growth hormone fusion protein and its application. The fusion protein hGH-linker-HSA and the hGH mutant fusion protein hGHmutF31Q / V90E-linker-HSA are constructed by connecting hGH and HSA through a connecting peptide. Mouse experiments show that hGHmutF31Q / V90E-linker-HSA can improve the metabolic stability of hGH, prolong the half-life of hGH, and enhance the administration effect of hGH, and has a broad application prospect in clinical practice.

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 an antibacterial peptide as well as a preparation method and application thereof. The amino acid sequence of the antibacterial peptide is LKVVFKVLFKRRR. The antibacterial peptide disclosed by the invention has relatively excellent antibacterial activity and metabolic stability and relatively low hemolytic activity and cytotoxicity, and is expected to become a novel antibacterial candidate drug. In addition, the antibacterial peptide is short in polypeptide sequence and only contains 13 amino acids, and all the amino acids are L-type amino acids, so that the antibacterial peptide is convenient to produce, low in production cost and beneficial to application and popularization. Generally speaking, the antibacterial peptide provided by the invention lays a foundation for further development of novel antibacterial drugs.

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 discloses a BimBH3 mimic peptide analogue of double-site coupling fatty acid, a preparation method of the BimBH3 mimic peptide analogue and application of the BimBH3 mimic peptide analogue serving as a novel PTPN1 inhibitor to development of long-acting hypoglycemic drugs. The structural general formula of the Bim BH3 mimic peptide analogue is as shown in formula I: # imgabs0 # mimic peptide compound is derived from a core region of a BimBH3 structural domain, the second amino acid is replaced and modified by Fmoc-Lys (Dde)-OH, the N end of a peptide chain is conjugated and modified by fatty monoacid or fatty diacid, the amino group of a side chain of lysine is conjugated and modified by fatty diacid, and the amino group of the side chain of lysine is conjugated and modified by fatty diacid. The compound has better metabolic stability, membrane permeability, pharmacokinetic characteristics and longer pharmacological action time, and shows an excellent long-acting hypoglycemic effect in the body of a type 2 diabetes mellitus model mouse. The compound is prepared by adopting a polypeptide solid-phase synthesis method, and a crude product is purified and freeze-dried to obtain a target compound.

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.