205 results about "Selective inhibition" patented technology

The present invention provides a compound of Formula Iand pharmaceutical compositions comprising one or more said compounds, and methods for using said compounds for treating or preventing one or more disease states that could benefit from inhibition of plasma kallikrein, including hereditary angioedema, uveitis, posterior uveitis, wet age related macular edema, diabetic macular edema, diabetic retinopathy and retinal vein occlusion. The compounds are selective inhibitors of plasma kallikrein.

The present invention relates to a substituted pyrimidine-fused ring inhibitor, a method for preparing same, and use thereof. Specifically, the compound of the present invention has a structure represented by formula (I). Further disclosed are a method for preparing the compound, and use of the compound as a KRAS mutation inhibitor. The compound has a good selective inhibition effect on KRAS mutation and has better pharmacodynamic and pharmacokinetic performance and lower toxic and side effects.

The present application relates to the technical field of medicine, in particular to the application of gansix triol A in the preparation of a drug for treating gastric cancer and / or non-small cell lung cancer, gansix triol A plays an anti-gastric cancer role by selectively inhibiting the proliferation of gastric cancer MGC-803 cells and inhibiting angiogenesis, the mechanism involves inhibiting the VEGF / VEGFR2 signal pathway and inducing cell apoptosis; the mechanism of gansix triol A in inhibiting the VEGF / VEGFR2 signal pathway is similar to that of bevacizumab; gansix triol A plays an anti-non-small cell lung cancer role by selectively inhibiting the proliferation of non-small cell lung cancer A549 cells, the mechanism involves inhibiting the MAPK / ERK signal pathway and inducing cell apoptosis. The present application finds that the cytotoxic activity of gansix triol A on MGC-803 cells and A549 cells is significantly stronger than that of tanshinone IIA; gansix triol A has an anti-tumor effect of "one drug with double targets, double inhibition" and "high efficiency and low toxicity".

Provided are a series of 5,6-dihydrothieno[3,4-h]quinazoline compounds as represented by formula (P) and pharmaceutically acceptable salts thereof, and the use of the compounds or pharmaceutically acceptable salts thereof in the preparation of solid tumor drugs, such as solid tumor drugs associated with selective PLK1 inhibitors.

Mcl-1 selective inhibitors, Bcl-2 selective inhibitors, and Mcl-1 / Bcl-2 dual inhibitors and methods of using the same for the treatment of disease are disclosed.

The present disclosure is directed to Hsp90 inhibitors having the Formula (I), subformulae thereof, pharmaceutically acceptable salts, stereoisomer, or tautomer thereof, and methods of use thereof.

Described are synthetic compounds having anti-inflammatory properties and optionally analgesic properties. These compounds are derivatives of FDA-approved anti-inflammatory, such as ibuprofen and indomethacin, and can be formed using reactions under microwave irradiation. Generally, the compounds contains a moiety of the parent drug, a triazolyl heterocycle, and a substituted or unsubstituted aryl group. In some forms, the compounds show anti-inflammatory properties and optionally analgesic properties with similar or higher efficiencies compared with their respective parent drugs, with additional advantages including no or reduced adverse effects (e.g., without ulcerogenic liability in the gastric) and / or selective inhibition of COX-2 over COX-1. Pharmaceutical compositions suitable for the delivery of the compounds to a subject in need thereof are disclosed. The pharmaceutical formulation can be administered by oral administration, parenteral administration, inhalation, mucosal administration, or a combination thereof. Methods for preventing or treating an inflammatory disease or disorder in a subject are also disclosed.

This application relates to a series of novel compounds that are selective inhibitors of phosphodiesterase type 9 ("PDE9") for the treatment of chronic heart failure. More specifically, this application relates to pyrazolo[3,4-d]pyrimidinone compounds for use in the treatment and prevention of chronic heart failure.

The present invention provides compounds represented by formula (I) and their racemates, stereoisomers, tautomers, isotopically labeled compounds, nitrogen oxides, solvates, polymorphs, metabolites, esters, prodrugs, or pharmaceutically acceptable salts thereof. These compounds have good FGFR2 / 3 inhibitory activity and can be used to treat or prevent FGFR2 / 3-mediated disorders and diseases, and can be used to manufacture drugs used for the treatment or prevention of such disorders and diseases. [Formula 1] TIFF2026518289000170.tif53170

Provided herein are pharmaceutical formulations of the AKT1 E17K selective inhibitor 4-((1-(4-(2-(2-aminopyridin-3-yl)-5-(5-fluoropyridin-2-yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)amino)pyrimidine-2-carbonitrile maleate.

This invention relates to the prevention and / or treatment of protein tyrosine kinase-mediated diseases, particularly phosphatidylinositol 3-kinase (PI3Ks)-mediated diseases. PI3Ks are well known as oncological targets, and several PI3K inhibitors have been developed that inhibit numerous class 1A PI3K isoforms. The development of selective inhibitors of PI3K-α may enable sufficient targeted inhibition while avoiding some of the known toxic drawbacks of pan-PI3K inhibitors. The inventors have discovered that a novel carbamoti-oil-pyrrolidine-carboxamide compound of formula (I) exhibits advantageous PI3K inhibitory activity, particularly with high selectivity for the isoform PI3K-α. In particular, this invention relates to the compound of formula (I), or deuterated or tritiated forms of the compound of formula (I), and pharmaceutically acceptable salts thereof. [Formula 1] The present invention also relates to pharmaceutical compositions containing a compound of formula (I) for use in the treatment and / or prevention of protein tyrosine kinase-mediated diseases, and to a compound of formula (I).

The present application provides 1H-imidazo[4,5-h]quinazoline compounds of Formula (I). The compounds are broad-spectrum inhibitors with strong activity against FLT3 kinase and are useful in the treatment of cell proliferative disorders.

The application discloses application of a PRMT3 inhibitor SGC707 in preparation of a drug for treating pulmonary fibrosis, and for the first time verifies that a selective PRMT3 inhibitor SGC707 can dose-dependently inhibit expression of fibrosis markers such as COL1A1 and alpha-SMA in fibroblasts induced by TGF-beta 1 in vitro; in a bleomycin (BLM) induced mouse pulmonary fibrosis model, SGC707 administration can significantly improve lung tissue collagen deposition, reduce inflammatory cell infiltration, repair alveolar structure damage, and effectively down-regulate expression levels of fibrosis related proteins in lung tissues. It is proved that PRMT3 is a functional target with important intervention value in pulmonary fibrosis, SGC707 has definite anti-pulmonary fibrosis activity in vitro and in vivo, and a new drug strategy is provided for treatment of pulmonary fibrosis.

The present disclosure provides compounds containing a 6-(pyrimidin-4-yl) quinoline structure, their use for the selective inhibition of CDK4 activity, and pharmaceutical compositions comprising the compounds as the treatment of various diseases, including cancer.

This invention generally relates to the field of therapeutic compounds. More specifically, this invention relates to 2-amino- N -(oxo-aryl-λ) 6 (-Thionyl)acetamide compounds (referred to herein as ANOSA compounds), said compounds In particular Inhibition (e.g., selective inhibition) of bacterial aminoacyl-tRNA synthetases (aaRS) (e.g., bacterial leucyl-tRNA synthetase, LeuRS). The present invention also relates to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions in vitro and in vivo to inhibit (e.g., selectively inhibit) bacterial aminoacyl-tRNA synthetases; to treat conditions improved by inhibition (e.g., selective inhibition) of bacterial aminoacyl-tRNA synthetases; to treat bacterial infections; and so on.

Disclosed herein are compounds of Formula (I) that are DGK inhibitors for activating T cells, promoting T cell proliferation, and / or exhibiting anti-tumor activity, methods of using the compounds disclosed herein to treat cancer, and pharmaceutical compositions comprising the compounds. In some embodiments, the compounds disclosed herein exhibit selective inhibitory activity of DGKα over DGKζ. In some embodiments, the compounds disclosed herein exhibit selective inhibitory activity of DGKζ over DGKα. TIFF2026505790000901.tif57165

The present invention provides an antibody or antigen-binding portion thereof that can bind to properdin (factor P). The antibody of the current invention leads to selective inhibition of alternative complement pathway while allowing the classical and lectin pathways to continue. Further, the antibody of the present invention may have modified or reduced binding to FcγRs to minimize its ADCC activity. The present invention provide an antibody that comprises an amino acid sequence to minimise its CDC activity. The antibody according to the present invention has higher FcRn binding affinity and therefore the antibody according to the present invention may have long circulating half-life in the body of the patient and it can be given at a reduced dosing frequency. The antibody according to the present invention can further be used in the preparation of a drug for treating diseases through inhibition of alternative complement pathway.

The application discloses a preparation method of an amido pyrazole compound and a method for preparing sildenafil by using the same. The amido pyrazole compound is shown as formula I. The compound of formula I is prepared by using 2-pentanone as an industrial chemical, and can be used for synthesizing sildenafil which is a selective inhibitor of type 5 phosphodiesterase (PDE5). The method has the advantages of easy availability of raw materials, simple operation, avoidance of nitration reaction, avoidance of safety hidden dangers caused by the nitration reaction from a technical source, and avoidance of environmental protection pressure caused by a large amount of nitration waste liquid, and is suitable for development into a green and sustainable production process of sildenafil bulk drug.

The invention relates to compounds of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a prodrug thereof, a deuterated molecule thereof or a PROTAC molecule thereof that selectively inhibit the activity of K-Ras G12D protein, compositions comprising the same, the methods of using the same and related intermediates.

This invention relates to deuterated 3-oxo-2,3-dihydropyridazine-4-carboxamide inhibitors, their preparation methods, and applications. Specifically, the compounds of this invention have the structure shown in formula (I). This invention also discloses the preparation method of the compounds and their use as AhR inhibitors. The compounds of this invention exhibit excellent selective inhibition of AhR and possess better pharmacodynamic and pharmacokinetic properties, as well as lower toxicity.

The present invention relates to a pharmaceutical composition comprising a metabolite of enavogliflozin, and a use thereof. An enavogliflozin M1 metabolite of chemical formula 1 is a SGLT1 / SGLT2 dual inhibitor and exhibits a different pharmacological mechanism from enavogliflozin which is a SGLT2 selective inhibitor. A pharmaceutical composition comprising, as an active ingredient, the enavogliflozin M1 metabolite that is a SGLT1 / SGLT2 dual inhibitor can be useful in the prevention or treatment of diabetes or heart failure.

The application discloses a chromone spiro compound, a preparation method and application thereof, and the chromone spiro compound is shown as formula I. The compound has selective CDK4 / 6 inhibitory activity, can relieve and / or treat myelosuppression caused by chemotherapy, improve weight loss caused by chemotherapy and improve survival rate, and has good drug safety. The compound has simple preparation method, is convenient for large-scale production, and has great application prospect.

The invention discloses application of alkalized tea saponin as a talc inhibitor, and belongs to the technical field of mineral separation. The molecular structural formula of the alkalized tea saponin is shown in the specification, wherein R is a sugar body unit; m is a cation; the alkalized tea saponin has a selective inhibition effect on flotation of talc, and is particularly suitable for flotation separation of metal sulfide ore (such as molybdenite, chalcopyrite, galena and sphalerite) and talc.

This invention discloses a type of click-type covalent drug, its regionally selective delivery system, and its applications. The invention comprises two parts: a click-type covalent drug and a tumor regionally selective delivery system. The click-type covalent drug consists of three parts: an azacyclic alkyne (DBCO), a small molecule drug, and a linker, having the structure of Formula 1. Optionally, the small molecule drug is a membrane protein inhibitor, an immunomodulator, or a chemotherapeutic drug. The click-type covalent drug reacts with azide-labeled target cells via a click reaction, forming a covalent bond that binds to the cell membrane, increasing the local drug concentration and prolonging the drug retention time, thereby enhancing selective inhibition of the target cells. The regionally selective delivery system is co-assembled from an amphiphilic block polymer and the click-type covalent drug for regionally selective delivery. This invention achieves covalent binding to azide-labeled tumor cells through the click-type covalent drug, while having no effect on unlabeled normal cells, reducing toxic side effects on normal tissues.

The present invention relates to an FGFR3 selective inhibitor compound or a pharmaceutically acceptable salt thereof. The compound can be used for treating cancer such as urothelial cancer, systemic sclerosis, fibrosis, pulmonary fibrosis, achondroplasia, thanatophoric dysplasia, severe achondroplasia with developmental delay and acanthosis nigricans, or Muenke syndrome.

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.

This invention provides a polypeptide and its applications. The amino acid sequence of the polypeptide is shown in SEQ ID NO: 1 or SE ID NO: 2; the 12th amino acid in the amino acid sequence of the polypeptide is alanine or glutamic acid; the 19th amino acid in the amino acid sequence of the polypeptide is methionine or leucine; the 28th amino acid in the amino acid sequence of the polypeptide is lysine or isoleucine; and the 29th amino acid in the amino acid sequence of the polypeptide is selected from isoleucine, leucine, and tryptophan. The polypeptide provided by this invention has good analgesic function and can selectively inhibit the activation of Nav1.7 channels, thereby inhibiting pain, which has extremely important clinical significance for pain disorders.