45 results about "Ester prodrug" patented technology

The invention discloses a derivative of a rice bran extract as well as a preparation method and application of the derivative. A C-3 benzoate prodrug system is constructed, the transmembrane absorption efficiency is remarkably improved by optimizing the oil-water partition coefficient, fixed-point slow release of active ingredients is achieved through inflammatory tissue esterase, and high bioavailability and low irritation are both considered. Meanwhile, C-25 fluorine atoms are introduced to serve as biological electron isosteres, and target affinity is enhanced by means of the unique electronic effect and polar hydrophobicity of the C-25 fluorine atoms; spatial conformation is locked through side chain saturation, so that the compound shows anti-inflammatory and tissue repair activity which is obviously superior to that of natural cycloartanol under the same dosage.

The present disclosure relates to methods of treating PTEN-deficient metastatic hormone- sensitive prostate cancer (mHSPC) in patients in need thereof, the methods comprising administering to the patients a combination comprising capivasertib or a pharmaceutically acceptable salt thereof; and abiraterone or an ester prodrug thereof, or a pharmaceutically acceptable salt thereof.

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

Provided in the present invention are compounds represented by formula (I) and racemates, stereoisomers, tautomers, nitrogen oxides, solvates, polymorphs, metabolites, esters, prodrugs, or pharmaceutically acceptable salts thereof. The compounds have good 17β-HSD1 inhibition effect, can be used for treating or preventing 17β-HSD1-mediated disorders and diseases, and can be used for preparing drugs for treating or preventing such disorders and diseases.

The invention discloses a nucleoside antiviral NHC diester prodrug as shown in a formula I and pharmaceutically acceptable salts thereof, and a preparation method and medical application of the nucleoside antiviral NHC diester prodrug. Pharmacological experiments prove that the compound disclosed by the invention has relatively strong inhibitory activity on replication of multiple RNA viruses. Particularly, the compound has good lung microsome release efficiency, the species difference of the lung release efficiency is small, the consistency of the in-vivo drug effect of the antiviral drug and the in-vivo drug effect of the antiviral drug can be improved, and the risk of species difference of prodrug release antiviral active ingredients is avoided. Therefore, the compound provided by the invention has good broad-spectrum antiviral activity, and can be used as a broad-spectrum antiviral drug for treating various respiratory virus infections.

Disclosed are a compound shown in formula I and racemate, stereoisomer, tautomer, isotopically labeled, nitroxide, solvate, polymorph, metabolite, ester, prodrug or pharmaceutically acceptable salt thereof, and a pharmaceutical composition comprising the same, a preparation method thereof, and a use thereof as a GHSR agonist in the preparation of a drug for the diagnosis, prevention and / or treatment of growth hormone-dependent diseases, the structure of formula I is as follows:

The invention provides a compound as shown in a formula (I) and a racemate, a stereoisomer, a tautomer, a nitrogen oxide, a solvate, a polymorphic substance, a metabolite, an ester, a prodrug or a pharmaceutically acceptable salt thereof, and the compound has a good p53-Y220C mutant activation effect and can be used for treating tumor diseases containing p53-Y220C mutant protein. And preparation of medicaments for such conditions or diseases.

Disclosed in the present invention are a compound represented by formula I, or a pharmaceutically acceptable salt thereof or an ester thereof, a prodrug thereof, an optical isomer thereof, a stereoisomer thereof, or a solvate thereof as an antagonist or an inhibitor for antagonizing and inhibiting a TRPV4-RhoA target, and use thereof in treating TRPV4-RhoA target-related diseases. The class of compounds exhibits an excellent effect of antagonizing TRPV4 and inhibiting RhoA activity, thereby laying a brand-new substance foundation for developing drugs for treating TRPV4-RhoA target-related diseases.

Provided are a compound represented by formula (I), and a racemate, a stereoisomer, a tautomer, an isotope label, a nitrogen oxide, a solvate, a polymorphic substance, a metabolite, an ester, a prodrug or a pharmaceutically acceptable salt thereof. The compound has a good FGFR2 / 3 inhibition effect, can be used for treating or preventing FGFR2 / 3 mediated diseases and diseases, and can be used for preparing medicines for treating or preventing the diseases and diseases.

The invention relates to an amino-acid ester prodrug of peramivir, which has the following structural formula: in the formula, R is L-valine, D-valine and L-isoleucine taking 2, 3-butanediol as a connecting arm, and L-isoleucine, L-alanine, L-valine or D-valine taking 2-methyl-1, 3-propylene glycol as a connecting arm. Mouse in-vivo pharmacokinetic verification shows that the amino-acid ester prodrug of the peramivir has remarkably higher absolute bioavailability and is suitable for being prepared into an oral administration preparation.

The invention belongs to the field of anti-infective drugs, discloses a compound for treating or preventing respiratory syncytial virus diseases, and provides compounds as shown in formulas (I-1) and (I-2) and pharmaceutically acceptable salts, esters, prodrugs, solvates, isomers or isotope forms thereof, the compound disclosed by the invention has antiviral activity and can be used for preparing a medicine for treating or preventing in-vivo virus infection of a subject susceptible to virus infection or experiencing virus infection.

The present application provides a compound shown in formula (I) and its racemate, stereoisomer, tautomer, isotopically labeled, nitroxide, solvate, polymorph, metabolite, ester, prodrug or pharmaceutically acceptable salt thereof. Such compounds have good FGFR2 / 3 inhibitory effect, and can be used for treating or preventing FGFR2 / 3 mediated disorders and diseases, and preparing drugs for treating or preventing such disorders and diseases.

The invention discloses application of a compound shown in a formula I or pharmaceutically acceptable salt or ester, a prodrug, an optical isomer, a stereoisomer or a solvate of the compound in prevention and treatment of obesity and related diseases thereof. The compound shows excellent effects of preventing and treating obesity and related diseases thereof, so that a brand new material basis is laid for developing medicines for preventing and treating obesity and related diseases thereof.

The invention relates to compounds according to Formula (I):wherein A is—As(OH)2 or an arsenoxide equivalent group; each of R1, R2, R3 and R4 is independently selected from H, X, OH, NH2, CO, SCN, —CH2NH, —NHCOCH3, —NHCOCH2X or NO, and X is a halogen; R5 is —NHCH2COOH, OH or OR6, wherein R6 is a C1-5 straight or branched alkyl group; and Z is a radioisotope with a half-life of less than 4 days, or a pharmaceutically acceptable salt, ester, prodrug or solvate thereof, uses of said compounds, and methods of preparing said compounds. The invention also relates to diagnostic methods utilizing said compounds.

The present application provides a compound represented by formula (I), or a pharmaceutically acceptable salt, ester, prodrug, complex, solvate, hydrate, or isomer thereof; and a use thereof in preparing drugs used to treat EZH2-mediated disease.

The invention belongs to the technical field of biological medicine, and particularly relates to a lamivudine prodrug long-acting PLGA microsphere preparation and a preparation method thereof. The lamivudine prodrug long-acting PLGA microsphere comprises a lamivudine fatty acid ester prodrug and a PLGA carrier material, the structural general formula of the lamivudine fatty acid ester prodrug is [lamivudine mother nucleus]-O-CO-(CH2) n-CH3, n is an integer of 4-18, and the lamivudine fatty acid ester prodrug is formed by connecting lamivudine and fatty acid through an amido bond; the microspheres are prepared by adopting a single emulsion solvent evaporation method, and the prepared microspheres have the advantages of high drug loading capacity (5%-11%), high encapsulation efficiency (36%-98%) and low burst release effect (24 h lt) by optimizing a prodrug structure, PLGA material characteristics and process parameters; 10%) and the like, and stable drug release of more than 4 weeks can be realized.

The invention provides a pharmaceutical active ingredient composition and application thereof in treating diabetes or preventing and treating diabetic complications. The pharmaceutical active ingredient composition provided by the invention comprises a first active ingredient and a second active ingredient, the first active component is at least one of the following components: a DPP-4 inhibitor, pharmaceutically acceptable salts, esters, prodrugs and metabolites thereof, and an SGLT-2 inhibitor, pharmaceutically acceptable salts, esters, prodrugs and metabolites thereof; the second active ingredient is at least one of the following components: coenzyme Q10, pharmaceutically acceptable ester of the coenzyme Q10, R-alpha-lipoic acid, pharmaceutically acceptable salt and ester of the R-alpha-lipoic acid, glutathione, pharmaceutically acceptable salt of the glutathione, resveratrol and pharmaceutically acceptable ester of the resveratrol. The pharmaceutical active ingredient composition provided by the invention has a good hypoglycemic effect, and has remarkable advantages in the aspects of relieving oxidative stress and preventing and treating diabetic complications.

The invention discloses a THK01 ester prodrug as well as a preparation method and application thereof in preparation of an anti-inflammatory drug, and the preparation method comprises the step of reacting THK01 with acyl chloride, anhydride or carboxylic acid in an organic solvent in the presence of a catalyst to obtain a THK01 esterified derivative. The THK01 esterified derivative disclosed by the invention is simple in synthetic route, high in reaction yield and easy to operate and implement; as a prodrug, the THK01 esterified derivative can effectively adjust the physicochemical properties (such as lipid-water partition coefficient) and transmembrane permeability of the compound, and shows typical ester prodrug characteristics in an in-vitro liver microsome experiment; in-vitro and in-vivo experiments show that the compounds can significantly inhibit NO generation and inflammatory reaction at low concentration, and the activity of the compounds is superior to that of positive control drugs, so that the compounds are expected to be developed into novel drugs for treating various inflammation-related diseases.

The invention discloses application of a compound as shown in a formula I, or pharmaceutically acceptable salt or ester, a prodrug, an optical isomer, a stereoisomer or a solvate of the compound as a TRPV4 inhibitor or antagonist and treatment of TRPV4 related diseases. The compound shows an excellent TRPV4 inhibitory activity effect, so that a brand-new material basis is laid for developing drugs for treating TRPV4 related diseases.

This invention discloses a combination drug of Akkermansia and an EET homologue and its uses, relating to the field of biomedical technology. Specifically, the combination drug of this invention comprises: A1) a first active ingredient, the first active ingredient comprising Akkermansia myxophilus; and A2) a second active ingredient, the second active ingredient comprising at least one of 14,15-epoxyeicosatetrienoic acid (14,15-EET) or an isomer of 14,15-epoxyeicosatetrienoic acid, a pharmaceutically acceptable salt, an ester, or a prodrug. The combination drug of this invention exhibits excellent anti-inflammatory and anti-tumor effects in LPS-induced inflammation models and LLC subcutaneous tumor models. The synergistic index SI > 1 calculated using the Bliss independent model indicates a good synergistic effect, and it can be used for the prevention, treatment, and prognostic improvement of non-small cell lung cancer.

This invention relates to a compound of formula (I), a pharmaceutically acceptable salt thereof or an ester prodrug thereof, and pharmaceutical compositions thereof for use in diseases or conditions associated with elevated lipoprotein (a) levels. The compounds of this invention exhibit strong lipoprotein (a) binding capacity and can effectively reduce the activity of lipoprotein (a) levels. Formula (I)

According to the ascorbyl palmitate prodrug micelle and the preparation method and application thereof, when the AP (at) PFPP polymer prodrug micelle is prepared, the micelle with the optimal size and particle size distribution can be formed when the molar ratio of FPBA to AP is 1: 2, and an in-vitro cell experiment shows that the AP (at) PFPP micelle can remove excessive ROS in cells and protect mitochondrial membrane potential; and human corneal epithelial cells (HECs) are protected from oxidative stress injury caused by hypertonic. Experimental results of a dry eye mouse model prove that the AP-PFPP micelle can effectively treat the dry eye, and the AP-PFPP prodrug micelle provides a new thought for the treatment of the dry eye.

The application relates to a cyclic icariin amino acid ester prodrug and a salt thereof, and belongs to the technical field of medicines, and particularly relates to a cyclic icariin amino acid ester prodrug formed between cyclic icariin and amino acids, a pharmaceutically acceptable salt thereof, and preparation and application thereof. Specifically, the application combines the structural characteristics of cyclic icariin and the inherent advantages of prodrugs, covalently combines amino acids with a 3-hydroxyl group in the structure of cyclic icariin to form a series of cyclic icariin amino acid ester prodrugs. The compound can significantly improve the water solubility, permeability and metabolic stability of cyclic icariin, improve the bioavailability of the medicine, and better exert an anti-tumor effect.

The present application relates to the use of hydroxyphenyl propionate compounds of formula (I), (II), (III), (IV) or (V) or pharmaceutically acceptable salts, solvates and / or ester prodrugs thereof for increasing anti-tumor immunity, to compositions comprising them, and to their use, for example, in cancer immunotherapy. More specifically, the present application relates to compounds useful in the treatment of diseases, disorders or conditions that can be treated by increasing the anti-tumor immunity of cells, such as cancer.

This invention relates to a series of 2'-deoxy-2',2'-difluorocytidine monophosphate amide derivatives (compounds of formula I) and methods for preparing their pharmaceutically acceptable salts, as well as their applications in the therapeutic field. Furthermore, this invention provides a series of novel, easily prepared, and highly active 2'-deoxy-2',2'-difluorocytidine-5'-monophosphate amide derivatives, namely ProTide, whose structure is mainly derived from the -5' hydroxyl group in the 2'-deoxy-2',2'-difluorocytidine structure to obtain the corresponding phosphate acyl amino acid ester prodrugs. These compounds exhibit good solubility and blood circulation stability, and can be used as single agents or in combination for the treatment of cancer diseases.

Provided in the present invention are a compound of general formula I or a pharmaceutically acceptable salt, a stereoisomer, an ester, a prodrug and a solvate thereof, a preparation method and use thereof, and in particular, the use of the compound of general formula I or the pharmaceutically acceptable salt, the stereoisomer, the ester, the prodrug and the solvate thereof as an HPK1 kinase inhibitor in the prevention and / or treatment of tumors and diseases caused by or associated with pathogen infection. The above-mentioned compound of general formula I contains at least one deuterium atom, and has high stability and good bioavailablility in an animal body.

The invention provides a carboxylesterase 2A covalent inhibitor as well as a preparation method and application thereof. The carboxylesterase 2A covalent inhibitor has a structure as shown in a formula I or a formula II. The carboxylesterase 2A covalent inhibitor provided by the invention can be specifically and covalently combined with serine residues in a mammalian carboxylesterase 2A catalytic center, so that the CES2A activity is highly selectively inhibited, and the carboxylesterase 2A covalent inhibitor shows a weak inhibition effect or no inhibition effect on other serine hydrolases. The half inhibitory concentration IC50 of the inhibitor on mammalian CES2A can reach a nano-friction level, and the inhibitor has good cell membrane permeability and metabolic stability. The inhibitor can effectively reduce intestinal toxicity caused by carboxylesterase 2A substrate drugs, and also can improve oral bioavailability of part of ester prodrugs.

The invention relates to a preparation method and anti-hepatic fibrosis application of a theanine derivative, the application further comprises treatment of chronic liver diseases such as alcoholic steatohepatitis and non-alcoholic steatohepatitis, and the structural formula of the theanine derivative is a compound shown as a formula I, the invention also relates to application of pharmaceutically acceptable salts or esters, prodrugs, stereoisomers, hydrates, solvates, crystal forms, metabolic forms of the pharmaceutically acceptable salts or esters, the prodrugs, the stereoisomers, the hydrates, the solvates and the crystal forms of the pharmaceutically acceptable salts or the pharmaceutically acceptable esters, the hydrates, the solvates and the crystal forms in preparation of medicines or reagents.

Provided in the present invention are the uses of an HPK1 inhibitor in preparation of drugs for preventing and / or treating human diseases or symptoms caused by pathogen infection or related to pathogen infection, and in preparation of drugs for preventing and / or treating tumors. The HPK1 inhibitor is a compound represented by following general formula I, or pharmaceutically acceptable salts, stereoisomers, esters, prodrugs, solvates and deuterated compounds thereof.

Chronic intractable pain is a global health issue, highlighting the need for a potent μ-agonist analgesic with minimal major side effects. Intrathecal administration of β-endorphin in humans produces significant analgesia without respiratory depression or tolerance. Earlier animal studies concluding that chronic administration of β-endorphin results in tolerance and respiratory depression may not be applicable to humans due to differences between human and animal μ-receptors and β-endorphins. It is anticipated that β-endorphin functions as a GPCR biased ligand, similar to ligand binding in endocrinopathies that do not usually produce tolerance. Ester prodrugs of β-endorphin are predicted to cross the human blood-brain barrier (BBB), undergo hydrolysis to β-endorphin and a non-toxic metabolite, and provide substantial analgesia with low toxicity and without major side effects. The synthesis of lead prodrugs is described. Compared to current pharmaceutical development expenditures, the risks associated with this research are considered low.