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

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 [<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 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.

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 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 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 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.

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 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.