34results about How to "Inhibits kinase activity" patented technology

The present invention provides a compound which is described commonly and is described in the subclass of the text and has the formula (I), wherein R<1>, R<2>, X<1>, X<2>, L<1>, L<2>, Y and Z are defined as the category and subclass of the text, the invention also provides the medical composition which is suitable to be used as protein kinase (such as Aurora) inhibitor and is suitable for treating the disease mediated by Aurora.

The invention relates to polyphenols substances, a synthesis method thereof and the use thereof, in particular to a flavonoid derivative, a preparation method thereof and the use thereof, and solves the problem that the conventional natural flavonoids compounds are difficult to extract and obtain and cannot be widely used. The structural formula (I) of an intermediate and the structural formula (II) of a final product are shown below, wherein R1, R2 and R3 are respectively selected from hydrogen, C1-C8 alkyl, halogen, nitro, C1-C8 alkoxy and amino; and R1, R2 and / or R3 can be fused with a benzene ring to form a substituted or unsubstituted fused ring compound; R4 and R5 are respectively selected from C1-C8 alkyl, C1-C8 alkoxy and alkylene; R may be H, methoxy-methoxy or methoxy; and b ring is a benzene ring or a heterocyclic compound. The derivative can be used for preparing medicaments for resisting tumors and cardiovascular and cerebrovascular diseases and inhibitors of protein tyrosine kinases, opens up a new way for preparing the medicaments and brings a new breakthrough to the medicament field; and the synthesis method has the advantages of mild condition and convenient operation.

The invention is directed to compounds of Formulae I and II: (I) (II) wherein R<1>, R<2>, R<3>, R<5>, R<6>, Y<1>, Y<2>, Y<3>, Y<4> and X are set forth in the specification, as well as solvates, hydrates, tautomers or pharmaceutically acceptable salts thereof, that inhibit protein tyrosine kinases, especially c-fms kinase.

The invention discloses essence with effects of whitening, defying age and activating skin and a preparation method of the essence. The essence comprises the following components: a wetting agent, acrylic (acrylate) / C10-30 alkyl acrylate crosslinked polymers, 2-oleamido-1,3-octodecanediol, mulberry bark extract, irkutsk anemone rhizome extract, persimmon leaf extract, growth-factor-containing lipidosome, capryloyl salicylic acid, cholesterol polyether-24, a thickening agent, a preservative and the balance of deionized water. The essence with effects of whitening, defying age and activating skin disclosed by the invention is scientific in ratio of various components, the various components achieve obvious synergistic effects, and the essence can achieve the effects of efficiently moisturizing, supplying nutrition to skin, promoting skin metabolism, reducing stains, effectively removing lines and wrinkles, retarding skin aging, improving skin sagging, brightening and tightening skin, moisturizing for a long time, enabling the skin to be moisturized, smooth and enriched in elasticity and improving the skin youth.

Isoquinoline compounds and their use as inhibitors of HPK1 (hematopoietic kinase 1) are described. The compounds are useful in treating HPK1 -dependent disorders and enhancing an immune response. Alsodescribed are methods of inhibiting HPK1, methods of treating HPK1 -dependent disorders, methods for enhancing an immune response, and methods for preparing the isoquinoline compounds.

The invention discloses an application of adenanthin in preparing medicines for preventing or treating multiple sclerosis, and an NF-kB inhibitor which is adenanthin. The adenanthin disclosed herein is safe, has low toxicity, and has strong pharmacological action and good medicinal foreground. The adenanthin active substance has the advantages of easy absorption, good stability, and the like, and is suitable for being as an additive of novel medicament, food, health products and / or meals for development.

The invention discloses 3-(4,5-substituted pyrimidinamine) phenyl derivatives and application thereof. The 3-(4,5-substituted pyrimidinamine) phenyl derivatives are compounds having a structure as shown in a formula (I) or pharmacologically acceptable salts of the compounds; the compounds or the salts thereof can be used for treating or preventing diseases or states of illnesses by means of certain mutant forms of epidermal growth factor receptors (EGFRs), can effectively inhibit the growth of multiple tumor cells and have an inhibiting effect for other protease of EGFR and Her families, thus being used for preparing antitumor drugs. The formula I is described in the description.

The invention discloses a method for eradicating color spots through melanin dissolution guide, wherein physical therapy is combined with drug therapy; an omnipotent spot clearing pen is dipped in melanin dissolution guide liquid and the melanin dissolution guide liquid is dispensed on the color spots through the omnipotent spot clearing pen; through the massage effect of the omnipotent spot clearing pen, the melanin dissolution guide liquid can quickly permeate into the color spots on the skin, thereby improving the absorption of the melanin dissolution guide liquid by the skin. Arbutin in the melanin dissolution guide liquid can be directly combined with tyrosinase so as to accelerate the decomposition and excretion of melanin and remove the color spots and freckles; salidroside and vitamin C ethyl ether sample can inhibit the tyrosine kinase activity so as to prevent the generation of the melanin and realize an effect of fading the spots; active ingredients in the melanin dissolution guide liquid soften the skin and thus improving the skin nourishing effect; moreover, the active ingredients also can be directly combined with the tyrosinase, then the decomposition and excretion of the melanin are accelerated, and the color spots are removed, thereby perfectly achieving the aims of removing spots, tendering skin and preserving moisture.

The invention provides a protein kinase polypeptide inhibitor PI-38. The amino acid sequence of the inhibitor is Ser-Gly-Arg-Val-Met-Arg-Gly-Pro-Arg-Ser-Ala. The polypeptide PI-38 can block interaction between protein p38MAPK and an effect protein of the protein p38MAPK and then specifically inhibit activity of kinase p38.

The present invention relates to compounds of formula (I) and their solvates, hydrates, tautomers or pharmaceutically acceptable salts for inhibiting protein tyrosine kinases, especially c-fms kinases, wherein A, R1, R2 , R3, R4, X and W are set forth in the specification.

The invention discloses a seed coating agent for preventing and treating rice bakanae disease. The seed coating agent is prepared from fludioxonil, tebuconazole, filler, a suspending aid, warning coloration, an anti-freezing agent, a preservative, a film-forming agent, a dispersing agent and water. The seed treatment agent is prepared by mixing a broad-spectrum contact bactericide and a triazole bactericide, and the product inhibits the growth of fungal mycelia through the comprehensive effects of inhibiting transfer related to glucose phosphorylation, inhibiting biosynthesis of ergosterol of fungi and the like, and finally causes pathogen death. The product has multiple prevention effects of protection, contact killing, treatment, eradication, internal absorption and the like. The product disclosed by the invention has a relatively good prevention and treatment effect on the rice bakanae disease.

The invention relates to a nitrogen-containing heterocyclic compound as well as a preparation method, a pharmaceutical composition and application thereof. The structural formula of the nitrogen-containing heterocyclic compound is shown in the specification, wherein Y and Z are respectively and independently selected from one of -CH and -N; the R1 and R2 are respectively and independently selected from one of a substituted aryl group, an unsubstituted aryl group, a substituted heteroaryl group and an unsubstituted heteroaryl group. On one hand, the nitrogen-containing heterocyclic compound is combined with a colchicine binding site of microtubule protein, so that microtubule depolymerization is promoted, and tumor cell proliferation is inhibited; on the other hand, the activity of kinase is inhibited by combining with an ATP binding site of protein kinase, so that proliferation and survival of tumor cells are inhibited at the same time through multiple channels. Compared with drugs such as paclitaxel aiming at tubulin, the compound has the advantages of better water solubility, simpler structure, easiness in synthesis and good drug resistance.

The invention relates to a polypeptide capable of specifically binding with the structural domain of PKR kinase and an application thereof. The invention relates to a 12-peptide sequence with amino acid sequence of Ser-Val-His-Leu-Tyr-His-Ser-Thr-Lys-Thr-Leu-Arg, which is capable of specifically binding with the PKR kinase structural domain (PKRcat) and inhibiting the activity of the PKR kinase. Therefore, the 12-peptide has practical value in research on the role of PKRcat in cell apoptosis and development of PKRcat inhibitors.

The invention discloses 3-(4,5-substituted pyrimidinamine) phenyl derivatives and application thereof. The 3-(4,5-substituted pyrimidinamine) phenyl derivatives are compounds having a structure as shown in a formula (I) or pharmacologically acceptable salts of the compounds; the compounds or the salts thereof can be used for treating or preventing diseases or states of illnesses by means of certain mutant forms of epidermal growth factor receptors (EGFRs), can effectively inhibit the growth of multiple tumor cells and have an inhibiting effect for other protease of EGFR and Her families, thus being used for preparing antitumor drugs. The formula I is described in the description.

The invention provides a protein kinase polypeptide inhibitor PI-38, an amino acid sequence of which is: Ser-Gly-Arg-Val-Met-Arg-Gly-Pro-Arg-Ser-Ala. The polypeptide PI-38 blocks the interaction of the p38MAPK protein with its effect protein, and specifically inhibits p38 kinase activity.

The invention discloses an ASK1 inhibitor, a derivative, a preparation method, a pharmaceutical composition and application thereof. The structure of the compound is shown as a formula I. The ASK1 inhibitor derivative relates to an isomer, a diastereoisomer, an enantiomer, a tautomer, a solvate, a salt of the solvate, a pharmaceutically acceptable salt or a mixture of the isomer, the diastereoisomer, the enantiomer, the tautomer and the solvate of the compound. The ASK1 inhibitor and the derivative thereof have an efficient inhibition effect on ASK1 kinase, and can be used for preparing drugsfor ASK1 kinase related diseases, the prepared drugs can play a drug effect at a molecular level and a cellular level, the application is wide, and the synthesis method of the compound is simple, convenient and easy to operate.

The invention discloses a Bcr-Abl amphiploid inhibitor and a preparation method and application thereof. The structural formula of compound or pharmaceutically acceptable salt of the compound is shown in the specification as I. The compound or pharmaceutically acceptable salt of the compound in the formula I serves as the Bcr-Abl amphiploid inhibitor, can effectively restrain activity of tyrosine kinase, can effectively used for treating diseases related to kinase abnormal excitation and has a good treatment effect on the malignant tumor. The preparation method of the Bcr-Abl amphiploid inhibitor is simple, convenient to implement and low in cost and has good application prospects.

The present invention discloses an isonicotinamide derivative represented by a formula (I) and a pharmaceutically acceptable salt thereof, wherein R1, R2, R3 and A are defined in the specification. The present invention further discloses a preparation method of the compounds, a drug composition containing the compound, and applications of the compounds in treatment of mammal, especially human overproliferation diseases and in preparation of drugs for treatment of mammal, especially human overproliferation diseases. The formula (I) is defined in the specification.

The invention provides a small-molecule inhibitor taking human LRRK2 protein as a target spot and application of the small-molecule inhibitor, and belongs to the technical field of pharmacy. According to the invention, a three-dimensional structure of the kinase structural domain of LRRK2 is constructed by taking the kinase structural domain of LRRK2 as a target and using a homologous modeling method, an I-type inhibitor binding pocket of the three-dimensional structure is selected, a Glide program is used for molecular docking, virtual screening is carried out from more than 1,600,000 compounds to obtain a small-molecule inhibitor LY2019-006 targeting human LRRK2 protein; and a kinase activity inhibition experiment is carried out, the inhibition effect of the compound LY2019-006 on the LRRK2 kinase activity is verified, the molecular dynamics simulation research is performed, and the action mechanism of the compound LY2019-006 and the target protein is clarified on the molecular level. The found small molecules and pharmaceutical salts thereof can provide a basis for research and development of new drugs for treating diseases related to LRRK2, such as Parkinson's disease, Alzheimer's disease, inflammatory bowel disease or Hansen's disease. The structure of the lead compound can be further optimized, and the lead compound has a good application prospect.

The invention discloses applications of V027-0576 in preparation of antitumor drugs. Through researches and discovery, the V027-0576 can effectively inhibit the proliferation of MDA-MB-231 cells; the IC50 value of the V027-0576 is 0.95 [mu]m; the inhibition effects of the V027-0576 is superior to the effects of most drugs for clinical treatment of breast cancer, such as cisplatin, gemcitabine, lapatinib, tamoxifen and 5-FU, gefitinib (of which IC50 values respectively are 21.9 [mu]m, > 40 [mu]m, 12.8 [mu]m, 18.9 [mu]m, 9.6 [mu]m and 7.3 [mu]m); and the V027-0576 is superior to a novel multi-target tyrosine kinase inhibitor DCC-2036 and an AXL specific inhibitor R428.

The invention discloses a substance having tyrosine kinase inhibition activity, a preparation method and an application, the substance is a compound having a structure of a general formula I, a geometric isomer and its medicinal salt, in a formula I, R1 is selected from hydrogen atom or -SO2NR3R4; R2 is selected from hydrogen atoms or nitro group; R3 and R4 are independently selected from hydrogen atoms, substituted or unsubstituted C1-12 straight chain or branched chain alkyl group, alicyclic group, aryl alkyl group, substituted or unsubstituted five or six-element monocyclic aromatic base, or condensed ring aromatic base, wherein, R3 and R4 can be same or different. The substance can confirm that the compounds have good tyrosine kinase inhibition activity by tyrosine kinase inhibition activity evaluation, and can be taken as a candidate medicine for preventing and treating tumor diseases.

The invention discloses a protein kinase inhibitor and derivatives thereof, a preparation method, a pharmaceutical composition and application. The compound structure of the protein kinase inhibitor is as shown in formula (I). The protein kinase inhibitor derivatives relate to an isomer, a diastereoisomer, an enantiomer, a tautomer, a solvate, a salt of the solvate, a pharmaceutically acceptable salt or a mixture thereof of the protein kinase inhibitor. The protein kinase inhibitor and the derivatives thereof have an efficient inhibition effect on protein kinase and can be used for preparing drugs for treating and / or preventing hyperproliferative diseases, virus-induced infectious diseases and / or cardiovascular diseases, and the prepared drugs can exert drug effects at the molecular level and the cellular level, and are wide in application. The synthesis method of the compound is simple and easy to operate.

The invention provides a protein degradation targeting chimera with a structure as shown in a general formula (I) defined in the description and application thereof. The protein degradation targeting chimera provided by the invention can effectively inhibit the kinase activity of Bcr-Abl and a Bcr-AblT315I mutant, can inhibit the expression of Bcr-AblT315I in tumor cells, has the function of degrading Bcr-AblT315I, has a better anti-proliferation effect on tumor cells carrying Bcr-Abl or Bcr-AblT315I, and can be used as a potential drug for anti-tumor treatment.

The invention relates to a polypeptide capable of specifically binding with the structural domain of PKR kinase and an application thereof. The invention relates to a 12-peptide sequence with amino acid sequence of Ser-Val-His-Leu-Tyr-His-Ser-Thr-Lys-Thr-Leu-Arg, which is capable of specifically binding with the PKR kinase structural domain (PKRcat) and inhibiting the activity of the PKR kinase. Therefore, the 12-peptide has practical value in research on the role of PKRcat in cell apoptosis and development of PKRcat inhibitors.

The invention provides a small-molecule inhibitor with human-derived LRRK2 protein as a target spot and application of the small-molecule inhibitor, belonging to the technical field of pharmacy. According to the invention, a kinase structural domain of LRRK2 is taken as a target, a three-dimensional structure of the kinase structural domain of LRRK2 is constructed by using a homologous modeling method, an I-type inhibitor binding pocket of the three-dimensional structure is selected, molecular docking is carried out by using a Glide program, and the small-molecule inhibitor LY2019-005 targeting the human-derived LRRK2 protein is virtually screened out from more than 160,000 compounds; a kinase activity inhibition experiment is carried out, so the inhibition effect of the compound LY2019-005 on the activity of LRRK2 kinase is verified; and molecular dynamics simulation research is carried out, and the action mechanism of the compound LY2019-005 and target protein is clarified at a molecular level. The found small molecule and a pharmaceutical salt thereof can provide a basis for research and development of novel drugs for treating diseases related to LRRK2, such as Parkinson's disease, Alzheimer's disease, inflammatory bowel disease or Hansen's disease. The structure of a lead compound can be further optimized, and the lead compound has good application prospects.

The invention provides novel FGFR inhibitors based on the pyridinylpyrimidine. The invention includes inhibitors with broad inhibitory activity against all FGFR isoforms, and inhibitors with selective inhibition against FGFR4. These novel pyridinylpyrimidine-based FGFR inhibitors, or their derivatives, have strong potential to be used to treat cancer.

The invention discloses a Bcr-Abl amphiploid inhibitor, a preparation method and an application thereof. A compound represented as the formula (I) or pharmaceutically acceptable salts thereof are provided in the invention. The compound represented as the formula (I) or the pharmaceutically acceptable salts thereof can be used as the Bcr-Abl amphiploid inhibitor which can effectively inhibit the activity of tyrosine kinase. The Bcr-Abl amphiploid inhibitor can be effectively used in treatment of diseases related to abnormal activation of the tyrosine kinase and has excellent treatment effect on malignant tumors. The inhibitor is easy to prepare, is low in cost and is excellent in application prospect.

The invention discloses a Bcr-Abl amphiploid inhibitor, a preparation method and an application thereof. A compound or pharmaceutically acceptable salts thereof provided in the invention can be used as the Bcr-Abl amphiploid inhibitor which can effectively inhibit the activity of tyrosine kinase. The Bcr-Abl amphiploid inhibitor can be effectively used in treatment of diseases related to abnormal activation of the tyrosine kinase and has excellent treatment effect on malignant tumors. The inhibitor is easy to prepare, is low in cost and is excellent in application prospect.