34results about How to "Improve pharmacokinetic properties" patented technology

The invention discloses a pyrimidoheterocyclic compound represented as the formula (I), or a pharmaceutically acceptable salt or a stereisomer thereof, or a prodrug molecule thereof. The pyrimidoheterocyclic compound can effectively inhibit growth of various tumor cells and has an inhibiting effect on EGFR protease. The pyrimidoheterocyclic compound can be used for preparing an anti-tumor drug, and can overcome drug resistance caused by medicines in the prior art, such as gefitinib, erlotinib and the like, has a selectivity on wild non-small cell lung cancer and is excellent in pharmacokinetic property.

The invention discloses a deuterated palbociclib derivative, and a preparation method and an application thereof. A structural formula of the deuterated palbociclib derivative is as shown in a formula (I), a formula (II), a formula (III) or a formula (IV). According to the deuterated palbociclib derivative disclosed by the invention, through selective deuteration of palbociclib, the pharmacokinetic property of the medicine is improved, thus the curative effect, the safety and the tolerance of the medicine are improved. According to the deuterated palbociclib salt disclosed by the invention, the solubility and the dissolution rate of the medicine are improved; a new compound is provided for synthesis of a novel anti-tumor medicine through synthesis of the deuterated palbociclib derivative; and the deuterated palbociclib derivative has similar biologic activity to the palbociclib, and has a good medicine application prospect.

The present invention discloses antitumor drug PEGylation and applications of the antitumor drug PEGylation in reversal of tumor multidrug resistance. The PEGylated antitumor drug is prepared by conjugating activated PEG onto an antitumor drug, and can be used for preparing the drug for reversal of tumor multidrug resistance. According to the present invention, the antitumor drugs (particularly water insoluble drugs) containing amino, carboxyl, hydroxyl and other modifiable groups are PEGylated so as to increase the water solubility, such that excellent characteristics of micelle self-assembly forming, production of invisible nanoparticles or active targeting tumor nanoparticles, drug release behavior regulation, system toxicity reducing, biological half-life improving, EPR effect production, tumor passive / active targeting production, tumor multidrug resistance reversal and the like are provided, and good clinical application prospects are provided.

The invention discloses a Thomsen-Friedenreich (TF) antigen and a TF antigen analogue and their chemoenzymatic synthesis method and use. The chemoenzymatic synthesis method comprises the following steps of 1, carrying out chemosynthesis of fluorogalactose and a fluoro-galactosamine analogue, 2, carrying out enzymatic synthesis of a fluoro-TF antigen, and 3, carrying out enzymatic synthesis of a sialyl TF antigen. The preparation method has flexibility of a chemosynthesis method, and high regioselectivity and high efficiency of an enzymatic synthesis method, creatively realizes enzymatic synthesis of the fluoro-TF antigen, and solves the problem that the existing fluoro-TF antigen chemosynthesis method has low substrate reactivity, complex synthesis steps and a low yield. A tumor-associated fluoro-carbohydrate antigen is superior to a natural carbohydrate antigen in pharmacokinetic properties and thus the preparation method has wide application prospects in development of a novel anti-tumor vaccine.

The invention discloses a [<18>F] AlF marked positron emission tomography (PET) polypeptide probe and a preparation method thereof. The probe comprises TMTP1 polypeptide and NOTA, which are connected together, and the structural formulae of the TMTP1 polypeptide and the NOTA are shown in the description. According to the [<18>F] AlF marked positron emission tomography (PET) polypeptide probe and the preparation method thereof, a glycine is added to the TMTP1, and a G-TMTP1 polypeptide is designed, so that the polypeptide does not influence the biological activity after being radioactively marked; furthermore, 18F is taken as a radionuclide, and the G-TMTP1 polypeptide is marked by utilizing a [<18>F] AlF-NOTA method, so that the obtained [<18>F] AlF-marked PET polypeptide probe has excellent pharmacokinetics properties, the background cleaning rate is high, the liver uptake rate is low, in-vivo stability is good, the uptake rate of tumor site is high, highly metastatic tumor can be diagnosed specifically, and the polypeptide probe can be applied to diagnosis or therapeutic evaluation of highly metastatic malignant tumor.

The present invention relates to the field of medicinal chemistry, and in particular relates to 18F-labeled ethinyloestradiol and a preparation method and application thereof, a modifying group is introduced into ethinylestradiol, and the ethinylestradiol is labeled by 18F, and the 18F-labeled ethinyloestradiol has good bioactivity, excellent pharmacokinetic properties and good stability in vitro, can be better targeting to breast cancer ER + cells, and can be used as a PET tracer for early diagnosis or therapeutic effect evaluation of high metastatic breast cancer ER + cells. The invention also provides the preparation method of the 18F labeled ethinylestradiol, a labeling group is introduced into the ethinylestradiol as a raw material by Click reaction, and heated for being exchanged with 18F<-> under relatively mild conditions, a labeling step and purification time are simplified, the radiochemical yield of the 18F-labeled ethinyloestradiol is high, and commercial application and clinical promotion of radiolabeled compounds are facilitated.

The invention discloses a nitrogen heterocyclic ring substituent containing benzoxazine oxazolidinone compound as well as a preparation method and application thereof in preparing medicines for treating and / or preventing mycobacterium tuberculosis caused infectious diseases. Specifically, the invention relates to a compound of formula (I) as shown in the specification, and a stereisomer thereof, apharmaceutically acceptable salt thereof, a medicinal composition with the compound, a use method thereof, and a medicine for preparing the compounds, wherein X1, X2, R1 and R2 are as shown in the specification.

The invention discloses a polypeptide for recognizing immune cells. The polypeptide comprises the following amino acid sequences: (a) an amino acid sequence of a C-terminal fragment sequence EQPDPGAVAAAAILRAILE containing human Triokinase / FMN cyclase; or (b) an amino acid sequence which is basically the same as the amino acid sequence in (a), and the basically the same means that the amino acid sequence in (a) has more than 80% of identity with that in (b). The invention also discloses a nucleic acid sequence for encoding the polypeptide; the polypeptide for targeted recognition of immune cells comprising the polypeptide and a polypeptide probe with a reporter group; a kit comprising the probe; and an application of the polypeptide or the probe in preparation of the kit for imaging livingcells of mammals.

Disclosed is a polypeptide that recognizes immune cells, the polypeptide comprising the following amino acid sequence: (a) an amino acid sequence containing C terminal fragment sequence EQPDPGAVAAAAILRAILE of human Triokinase / FMN cyclase and the homologous sequence thereof; or (b) an amino acid sequence in which the amino acid sequence is substantially the same as described in (a), the substantially the same referred to amino acid sequence having at least 80% sequence identity to the amino acid sequence as described above in (a). Also disclosed in the present invention are a nucleotide sequence encoding the polypeptide; a polypeptide probe that targets recognized immune cells, comprises the polypeptide as described above and has a reporter group; a kit comprising the above-mentioned probe;and the use of the polypeptide or probe as described above in the preparation of the kit for mammalian living cell imaging.

The invention discloses polypeptide for target identification of immunocyte. The polypeptide comprises following amino acid sequences: (a) an amino acid sequence of a C terminal fragment sequence AILEVLQS containing human Triokinase / FMN cyclase of and a homologous sequence of the amino acid sequence; or (b) an amino acid sequence which is basically the same as the amino acid sequence as shown in (a), wherein the basic same meaning lies in that the amino acid sequence in (a) has 70% or above of sequence identity. The invention further discloses a nucleic acid sequence for coding the polypeptide, a polypeptide probe for target identification of immunocyte, containing the polypeptide and with a reported group, and a reagent kit comprising the probe, and applications of the polypeptide or theprobe.

The invention relates to a compound which is inhibitor for replication of one or multiple types of hepatitis c viruses. In addition, the invention discloses a medicinal component and preparation containing the compound and application of the inhibitor for replication of the hepatitis c viruses. The compound can be used individually or used with other compounds to treat symptoms caused by infection of the hepatitis viruses.

The invention belongs to the technical field of pharmaceutical compounds and particularly relates to a deuterated palbociclib derivative and preparation method and application thereof; the deuterated palbociclib derivative has a structure shown as in formula (I); by selectively deuterating active metabolic sites of palbociclib, the metabolic nature of a pharmaceutical is improved, and the therapeutic effect, safety and durability of the pharmaceutical are improved accordingly; through the synthesis of the deuterated palbociclib derivative, a novel compound is provided for synthesizing a novel antitumor pharmaceutical; this compound is applicable to the inhibitor pharmaceutical aspect to inhibit cyclin dependent kinase 4 and / or 6, and the aspect of pharmaceuticals for treating breast cancer, ovarian cancer, liver cancer or acute lymphoblastic leukemia.

The invention belongs to the technical field of medicines, and particularly relates to a pharmaceutical composition for preventing and / or treating cancers. The invention relates to a medicine composition, in particular to a medicine composition containing a CDK4 / 6 inhibitor compound shown in a formula (I) or pharmaceutically acceptable salt thereof and a second treatment reagent or pharmaceutically acceptable salt thereof, application of the medicine composition in preparation of medicines for preventing and / or treating cancers and a medicine box containing the medicine composition.

The invention provides a compound serving as a hexanokinase inhibitor and application of the compound. The compound comprises 2-(1-methyl-3-(2-((S)-2-methyl azetidine-1-yl)-6-(trifluoromethyl) pyrimidine-4-yl)-3-azabicyclo [3.1. 0] hexane-6-yl) acetic acid, 2-(1, 5-dimethyl-3-(2-((S)-2-methyl azetidine-1-yl)-6-(trifluoromethyl) pyrimidine-4-yl)-3-azabicyclo [3.1. 0] hexane-6-yl) acetic acid and the like. The compound has good application in preparation of drugs for treating diseases such as T1D, T2D, LADA, EOD, YOAD, MODY, malnutrition-related diabetes mellitus, gestational diabetes mellitus and the like.

The invention belongs to the field of chemical medicine, and particularly relates to benzyl-1H-pyrazole and benzyl-1H-pyrazole derivatives, and a preparation method and application thereof. The structure of the benzyl-1H-pyrazole and benzyl-1H-pyrazole derivatives is disclosed as Formula I. The invention also provides a preparation method and application of the benzyl-1H-pyrazole and benzyl-1H-pyrazole derivatives. The benzyl-1H-pyrazole and benzyl-1H-pyrazole derivatives provided by the invention have obvious inhibiting activity for RIP1 kinase, and have obvious effects on in-vivo therapy of ischemic myocardial cell necrosis. The derivatives have favorable solubility, and have greatly higher properties than the Nec-series compounds in the aspects of curative effect and pharmaceutical properties. The synthesis method of the benzyl-1H-pyrazole and benzyl-1H-pyrazole derivatives is simple, and is suitable for large-scale production.

The invention falls within the technical field of pharmaceutical compounds, and in particular relates to a deuterated palbociclib derivative, a preparation method and the use thereof. The deuterated palbociclib derivative has a structure as shown in formula (I); by selectively deuterating active metabolic sites of palbociclib, the metabolic nature of a drug is improved, and the efficacy, safety and tolerance of the drug are improved accordingly. The synthesis of the deuterated palbociclib derivative provides a new type of compound for the synthesis of a new type anti-tumour drug; and such a compound can be used in the application of the inhibitor drug for inhibiting cyclin dependent kinases 4 and / or 6, and in the application of drugs for treating breast cancer, ovarian carcinoma, liver cancer or acute lymphoblastic leukemia.

The invention belongs to the field of chemical pharmaceuticals, and particularly relates to a benzyl-1H-pyrazol and benzyl-1H-pyrrole derivative and a preparation method and application thereof. The structure of the benzyl-1H-pyrazol and benzyl-1H-pyrrole derivative is as shown in a formula I. According to the benzyl-1H-pyrazol and benzyl-1H-pyrrole derivative, the inhibitory activity on RIP1 kinase is significant, and the effect of treating ischemic myocyte necrosis in vivo is obvious. The solubility of the derivative is good, and the curative effect and pharmacokinetic property are greatly improved compared with Nec serial compounds. Meanwhile, the benzyl-1H-pyrazol and benzyl-1H-pyrrole derivative is simple in synthesis method and suitable for large-scale production. Please see the formula I in the description.

The invention relates to an octahydropyrrolo[3,4-c]pyrrole derivative and use thereof. The compound disclosed by the invention and a pharmaceutical composition containing the compound are used for antagonizing orexin receptors. The invention further relates to methods for preparing the compound and the pharmaceutical composition and use of the compound and the pharmaceutical composition in treatment or prevention of diseases related to the orexin receptors.

This invention provides caspase inhibitors of formula (I): wherein Z is oxygen or sulfur; R<1> is hydrogen, -CHN2,R, CH2OR, CH2SR, or -CH2Y; Y is an electronegative leaving group; R<2> is CO2H, CH2CO2H, or esters, amides or isosteres thereof; R<3> is a group capable of fitting into the S2 subsite of a caspase enzyme; R<4> and R<5> are taken together with the intervening nitrogen to form heterocyclic ring and R is as described in the specification. The compounds are effective inhibitors of apoptosis and IL-1 beta secretion.

The invention discloses a tumor stroma developer, which has a chemical structural formula disclosed in the invention: wherein R is hydrogen or fluorine. Compared with the prior art, the tumor stroma developer has the advantages that the tumor stroma developer shows obvious affinity to FPA, the intake amount of the tumor stroma developer for FAP high-expression malignant tumors in the tumor stroma is high, the tumor stroma developer has high sensitivity and specificity for diagnosis of the malignant tumors, and false positive does not occur easily, so that the tumor stroma developer can be effectively and safely applied to diagnosis and treatment of various malignant tumors; the half-life period is longer, the window period is prolonged, and clinical use is more facilitated.

The invention discloses a tripterine derivative, biogenetic salt of the derivative, and a preparation method and application of the biogenetic salt. The tripterine has a structure as shown in the specification. The biogenetic salt of the tripterine derivative is prepared by mixing and reacting the tripterine derivative with medicinally acceptable inorganic acid or organic acid. The tripterine derivative and the biogenetic salt of the tripterine derivative can be used for preparing medicines for resisting hepatic fibrosis. A nitrogen-containing hydrophilic group is introduced into C-28 position carboxylic acid and the tripterine derivative is salinized, so that the pharmacokinetic property is improved obviously, the bioavailability is improved, and the safety is improved.

The invention relates to novel cyclic phospholipids, pharmaceutically acceptable salts or esters thereof and a medicine composition used for treating HCV infection. Chlorine in a phenyl ring of a Hepdirect cyclic phospholipid prodrug is replaced by a specific ring, thus effectively reducing toxicity, eliminating potential cancer risks and basically maintaining or even improving drug metabolism characteristics and in-vivo activity. Compared with a Hepdirect cyclic phospholipid, the novel cyclic phospholipids, the salts or esters and the composition are ideal clinical treating agents.

The invention belongs to the field of medicinal chemistry, and relates to a heterocyclic compound and a preparation method, a pharmaceutical composition and application thereof. Particularly, the invention relates to a heterocyclic compound as shown in a formula I, a pharmaceutical composition containing the heterocyclic compound and application of the heterocyclic compound as an SHP2 inhibitor in the field of medicine. The heterocyclic compound provided by the invention shows excellent biological activity and druggability, and has great drug development prospects.

The invention discloses a tanshinol amide derivative and a preparation method and application thereof. A structural general formula of the tanshinol amide derivative is shown as a general formula (I) and a general formula (II). The tanshinol amide derivative can be used for preparing medicines for treating the ischemic cerebrovascular disease and the vascular dementia.

The invention discloses a salt of a benzo-thiopyrone compound, and particularly relates to a salt of 2-(4-(cyclohexylmethyl)piperazine-1-yl)-6-(trifluoromethyl)-8-nitro-benzo-thiopyrone-4-one shown asa formula (I), a preparation method of the salt and an application of the salt in medicines for treating and / or preventing infectious diseases caused by mycobacterium tuberculosis. In particular, thepresent invention relates to pharmaceutically acceptable salts of formula (I) and pharmaceutical compositions comprising the compounds of the invention. The invention aims to prepare a salt of 2-(4-(cyclohexylmethyl)piperazine-1-yl)-6-(trifluoromethyl)-8-nitro-benzothiopyran-4-one with remarkably improved pharmacokinetic properties and physicochemical properties and strong mycobacterium tuberculosis resisting activity, and the salt can be used as a potential new drug and can be used for treating infectious diseases caused by bacteria, and especially used for treatment or prophylactic treatment of pulmonary tuberculosis (TB) diseases caused by Mycobacterium tuberculosis, in particular Mycobacterium tuberculosis, while at the same time being useful for overcoming problems associated with drug resistance of Mycobacterium tuberculosis.

The invention belongs to the technical field of medicines, relates to an antitumor drug cabazitaxel-fatty acid conjugate as well as a preparation method and application thereof, and further relates to a nano preparation of the cabazitaxel-fatty acid conjugate and application thereof. The fatty acid is oleic acid or linoleic acid. In the cabazitaxel-fatty acid conjugate disclosed by the invention, hydroxyl of cabazitaxel is connected with carboxyl of oleic acid or linoleic acid through a disulfide bond. The cabazitaxel-linoleic acid conjugate or the cabazitaxel-linoleic acid conjugate can be self-assembled into nanoparticles, and the preparation is simple in preparation process and easy to industrialize; the sensitive drug release of the intracellular environment of a tumor part can be realized, the anti-tumor cell activity is higher, and the in-vivo pharmacokinetic property is better; most importantly, the nano preparation shows higher in-vivo tumor inhibition activity, and shows a more excellent in-vivo safety effect of the preparation at the same time.