Abstract: Disclosed herein are compounds that are inhibitors of BDR4 and their use in the treatment of cancer. Methods of screening for selective inhibitors of BDR4 are also disclosed. In certain aspects, disclosed are compounds of Formula I, II, and II.

Abstract: The present invention provides compounds of Formula (I): wherein all variables are as defined in the specification, and compositions comprising any of such novel compounds. These compounds are APJ agonists which may be used as medicaments.

Abstract: This invention relates to a preventive and/or therapeutic agent for sarcopenia, comprising a prostaglandin D2 production inhibitor as an active ingredient.

Abstract: Disclosed are compounds active towards nuclear receptors, pharmaceutical compositions containing the compounds and use of the compounds in therapy.

Abstract: The present invention relates to pyrrolo-aromatic heterocyclic compounds, a preparation method therefor and medical use thereof. Particularly, the present invention relates to a compound represented by formula I, a preparation method therefor, a pharmaceutical composition comprising the compound, and use of the compound as a BTK kinase inhibitor. The compound and the pharmaceutical composition comprising same can be used for the treating diseases associated with BTK kinase activity, such as inflammations, autoimmune disorders, and cancers. The definition of each substituent in formula I is the same as that in the description.

Abstract: Compounds within the scope of the present invention have a Formula 1 or a salt or produg thereof, where ring A is selected from cycloaliphatic; ring B is aryl; R1 is selected from (C1-C10)alkyl, (C3-C10)cycloalkyl, halo, aryl, and heteroaryl; and R2 and R3 are independently selected from hydrogen and (C1-C6)alkyl. Disclosed compounds may have an IRAK4 IC50 of from 0.003 ?M to 3.7 ?M; a TAK1 IC50 of from 0.008 ?M to 132 ?M; and/or an IRAK4/TAK1 selectivity of from 1 to 450. Particular compounds may have an IRAK4/TAK1 selectivity of from 100 to 500. Disclosed compositions may be formulated as pharmaceutical compositions. A method for using the compounds and/or compositions also are disclosed. The method may comprise administering to a subject an effective amount of a compound within the scope of the present invention, particularly to selectively inhibit IRAK 1 and/or IRAK4 over TAK1.

Abstract: The present invention provides methods and compositions for treating and preventing lung injuries due to or associated with coronavirus infections that cause Severe Acute Respiratory Syndrome, including COVID-19. More specifically the present invention provides methods for treating or preventing the lung injuries associated with SARS-CoV-2 infections, such as acute lung injury (ALI), lung fibrosis, and acute respiratory distress syndrome (ARDS). The methods comprise administering a therapeutically effective amount of a pharmaceutical composition comprising a protein kinase inhibitor compound having MAP3K2/MAP3K3 inhibition activity, such as pazopanib or nintedanib, or a pharmaceutically acceptable salt, solvate, or prodrug thereof, to a patient in need thereof. The present invention also provides devices for administering the compositions.

Abstract: The present invention relates to a novel compound exhibiting enteropeptidase-inhibiting activity, a pharmaceutically acceptable salt thereof, a pharmaceutical composition for preventing and treating metabolic diseases such as obesity, diabetes mellitus or hyperlipidemia, etc. comprising the compound or pharmaceutically acceptable salt, and a method for preventing or treating metabolic disease using the above novel compound. The compound of the present invention has excellent inhibitory activity against enteropeptidase, and thus is not absorbed into the body, but are excreted outside the body. However, since not only fat but also protein are discharged together, it has few side effects such as fat stools and acts only in the gastrointestinal tract, so it has few side effects such as depression, and is very useful as a therapeutic or prophylactic drug for various metabolic diseases such as obesity, diabetes mellitus, and hyperlipidemia.

Abstract: Compounds having formula (I), and enantiomers, and diastereomers, stereoisomers, pharmaceutically-acceptable salts thereof, (I) are useful as kinase modulators, including RIPK1 modulation. All the variables are as defined herein.

Abstract: The disclosure relates to pharmaceutical combinations comprising an HDAC6 selective inhibitor and a JAK1/2 inhibitor for the treatment of a cancer, such as a hematological cancer, in a subject in need thereof. Also provided herein are methods for treating a cancer in a subject in need thereof, comprising administering to the subject an effective amount of an HDAC6 selective inhibitor and a JAK1/2 inhibitor.

Abstract: The present invention provides compounds of Formula (I): wherein all variables are as defined in the specification, and compositions comprising any of such novel compounds. These compounds are APJ agonists which may be used as medicaments.

Abstract: A novel class of inhibitors of protein kinases useful in the treatment of proliferative cell diseases and conditions including cancers, and especially those characterised by over-expression of CDK8 and/or one or more aberrant CDK8 activity, including certain cancers of lung, breast, brain, ovary, prostate, colorectal cancer and leukaemias. The inhibitors have the general structure I.

Abstract: The present disclosure relates to a class of pyrimidine derivatives having immunomodulating properties that act via TLR7 which are useful in the treatment of viral infections and cancers.

Abstract: A series of 2-imino-6-methyltetrahydropyrimidin-4(1H)-one derivatives, substituted in the 6-position by a phenyl moiety which in turn is meta-substituted by an optionally substituted unsaturated fused bicyclic ring system containing at least one nitrogen atom, being selective inhibitors of plasmepsin V activity, are beneficial as pharmaceutical agents, especially in the treatment of malaria.

Abstract: The present disclosure provides a compound of Formula (I) or pharmaceutically acceptable salt, stereoisomers thereof, a pharmaceutical composition comprising the compound, and a method to treat or prevent neurodegenerative diseases using the compound.

Abstract: A particulate plug for removing a preservative from a solution, suspension, or emulsion comprising a drug is presented. The plug comprises microparticles of a homopolymer comprising a hydrophilic repeating unit or of a copolymer comprising at least one hydrophilic repeating unit and at least one hydrophobic repeating unit. The microparticles are irregular-shaped rigid aggregates and are sized and packed to yield a hydraulic permeability greater than 0.01 Da. The homopolymers have absorbed portions of a preservative to be removed and/or a drug for delivery in solution, as can the copolymer.

Abstract: The present invention provides compounds that can modulate the amount of Nav1.7 protein, a key protein in pain signaling, that is present in the cellular surface and methods for using such compounds. In particular, compounds of the invention modulate the amount of Nav1.7 protein on the cellular surface by modulating SUMOylation of CRMP2. Thus, compounds of the invention can be used to treat various clinical conditions associated with the presence and/or activation of Nav1.7 protein on the cellular surface and/or SUMOylation of CRMP2.

Abstract: Tartrate salts of the compound of structure (I), crystalline forms thereof, and therapeutic applications thereof for treating solid tumors (e.g., advanced solid tumor) or hematopoietic cancers. Also provided herein are methods for synthesizing the tartrate salts and the crystalline forms thereof.

Abstract: Provided herein are heterocyclic derivative compounds of Formula (I) and pharmaceutical compositions comprising said compounds. The compounds of Formula (I) are useful for inhibiting plasma kallikrein. Furthermore, the disclosed compounds and compositions are useful for the treatment of diseases wherein the inhibition of plasma kallikrein inhibition has been implicated, such as angioedema and the like.

Abstract: The invention relates to compounds and their use in the treatment of disease. Novel irreversible inhibitors of wild-type and mutant forms of EGFR, FGFR, ALK, ROS, JAK, BTK, BLK, ITK, TEC, and/or TXK and their use for the treatment of cell proliferation disorders are described.

Abstract: Tartrate salts of the compound of structure (I), crystalline forms thereof, and therapeutic applications thereof for treating solid tumors (e.g., advanced solid tumor) or hematopoietic cancers. Also provided herein are methods for synthesizing the tartrate salts and the crystalline forms thereof.

Abstract: Disclosed are substituted aromatic N-heterocyclic compounds. The disclosed compounds typically exhibit kinase inhibition activity, for example, and inhibit Mnk1 kinase and/or Mnk2 kinase. The disclosed compounds may be used in pharmaceutical compositions and methods for treating diseases or disorders associated with Mnk1 kinase activity and/or Mnk2 kinase activity, such as cancers, diabetes, autism, and fragile X syndrome.

Abstract: A phosphoramidochloridate morpholino monomer of the following formula is provided:

Abstract: A 2-substituted aromatic ring-pyrimidine derivative as shown in a general formula I, and an optical isomer or a pharmaceutically acceptable salt or a solvate thereof are provided. The present invention designs and synthesizes a series of novel small molecular Chk1 inhibitors by using N-substituted pyridin-2-aminopyrimidine obtained through structure-based virtual screening as a lead compound, and carries out Chk1 kinase inhibitory activity test. The experiment confirmed that said compounds possess strong anti-cancer effect, Chk1 kinase inhibitory activity and are promising Chk1 inhibitors. The compounds can be used as new cancer therapeutic drugs, which can be applied to treat solid tumors or hematologic tumors related to proliferative disease of human or animal.

Abstract: The invention provides a compound of formula: or a salt thereof, wherein the variables RAA, n, ring A, ring B, R1a, R1b, R2, R3, R4, R5, R6, R7, R8, and R9 have the meaning as described herein, and compositions containing such compounds and methods for using such compounds and compositions.

Abstract: Provided herein are methods and intermediates for making (1R,2R,5R)-5-amino-2-methylcyclohexanol hydrochloride, which are useful for the preparation of compounds useful for the treatment of a disease, disorder, or condition associated with the JNK pathway.

Abstract: Provided are compounds of the formula: and pharmaceutically acceptable salts and compositions thereof, which are useful for treating a variety of diseases, disorders or conditions, associated with potassium channels.

Abstract: Provided herein are isotopologues of Compound A, which are enriched with isotopes such as, for example, deuterium. Pharmaceutical compositions comprising the isotope-enriched compounds, and methods of using such compounds are also provided.

Abstract: The FGFR-encoding gene was studied extensively with regard to its expression, hyperamplification, mutation, translocation, or such in various cancer cells. As a result, novel fusion polypeptides in which the FGFR3 polypeptide is fused with a different polypeptide were identified and isolated from several types of bladder cancer-derived cells and lung cancer cells. The use of a fusion polypeptide of the present invention as a biomarker in FGFR inhibitor-based cancer therapy enables one to avoid side effects in cancer therapy and control the therapeutic condition to produce the best therapeutic effect, thereby enabling individualized medicine.

Abstract: The present invention provides novel heteroaryl compounds, pharmaceutical acceptable salts and formulations thereof. They are useful in preventing, managing, treating or lessening the severity of a protein kinase-mediated disease. The invention also provides pharmaceutically acceptable compositions comprising such compounds and methods of using the compositions in the treatment of protein kinase-mediated disease.

Abstract: The present invention relates to a 6-phenoxypyrimidine derivative, a method for preparing the compound and a pharmaceutical composition containing the compound as an active ingredient. Because the 6-phenoxypyrimidine compound represented by Chemical Formula 1 according to the present invention has an activity of inhibiting the production of nitric oxide (NO) as an inflammation-related factor, it is useful in treating and preventing inflammatory diseases including immunological diseases.

Abstract: The present invention provides compounds useful as inhibitors of Btk, compositions thereof, and methods of using the same.

Abstract: The present disclosure concerns at least one entity chosen from compounds of Formula (I) and pharmaceutically acceptable salts thereof: wherein the variable groups X, R1, R2, R3 m, n and p are as defined herein. The present disclosure also relates to methods for the preparation of at least one such entity, and intermediates useful in the preparation thereof, to pharmaceutical compositions containing at least one such entity, to the use of at least one such entity in the preparation of medicaments, and to the use of at least one such entity in the treatment of conditions such as, for example, allergic diseases, autoimmune diseases, viral diseases, and cancer.

Abstract: A number of crystalline forms of N-(2-((6-(3-(2,6-dichloro-3,5-dimethoxyphenyl)-1-methylureido)pyrimidin-4-yl)amino)-5-(4-ethylpiperazin-1-yl)phenyl)acrylamide are provided. These include a crystalline free base form, a crystalline monohydrochloride salt form, a crystalline dihydrochloride salt form, and a crystalline ethanesulfonate salt form. Methods of making and using crystalline compounds are also provided.

Abstract: A method for preparing 5-(4-bromophenyl)-4,6-dichloropyrimidine is provided. The method comprises the steps of: preparing methyl p-bromophenylacetate (Intermediate I) by catalytic esterification of p-bromophenylacetic acid, and then reacting with dimethyl carbonate to synthesize 2-(4-bromophenyl)-malonic acid-1,3-dimethyl ester (Intermediate 2), cyclizing with formamidine hydrochloride to obtain 5-(4-bromophenyl)-4,6-dihydroxypyrimidine (Intermediate 3), and then chlorinating to give the product 5-(4-bromophenyl)-4,6-dichloropyrimidine. In the process of preparing Intermediate 1 in the present invention, a solid acid is used as a catalyst. Moreover, in the process of preparing Intermediate 2, sodium methoxide is used as a base in place of sodium hydride or sodium amide used in the prior art. Furthermore, Intermediate 3 is prepared by a one-pot process.

Abstract: This invention relates to antagonists of Kinase Suppressor of Ras (KSR). Pharmaceutical compositions comprising KSR inhibitors and methods of treating cancer are also provided.

Abstract: The present invention provides methods of treating cancer, particularly cancers that had developed resistance to PD-1 and PDL-1 blockade. Also included are methods of identifying therapeutic targets for the treatment of cancer.

Abstract: Crystal Form I of 5-chloro-6-(2-iminopyrrolidin-1-yl)methyl-2,4(1H,3H)-pyrimidinedione hydrochloride exhibiting powder X-ray peaks at two or more angles selected from the group consisting of 11.6°, 17.2°, 17.8°, 23.3°, 27.1°, and 29.3° as a diffraction angle (2?±0.2°).

Abstract: A method for treating cancer in patients with creatinine clearance of 15 mL/min or more and less than 30 mL/min, including dividing a combination drug containing ?,?,?-trifluorothymidine (FTD) and 5-chloro-6-[(2-iminopyrrolidine-1-yl)methyl]pyrimidine-2,4(1H,3H)-dione hydrochloride in a molar ratio of 1:0.5, in a dose of 30 to 50 mg/m2/day as FTD-equivalent, into two to four times a day, and orally administering it to the patient.

Abstract: The present invention discloses compounds of Formula (I), or pharmaceutically acceptable salts, esters, or prodrugs thereof: X-A-Y—Z-L-R1??(I) which inhibit the protein(s) encoded by hepatitis B virus (HBV) or interfere with the function of the HBV life cycle of the hepatitis B virus and are also useful as antiviral agents. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from HBV infection. The invention also relates to methods of treating an HBV infection in a subject by administering a pharmaceutical composition comprising the compounds of the present invention.

Abstract: The present invention provides compounds that can modulate the amount of Nav 1.7 protein, a key protein in pain signaling, that is present in the cellular surface and methods for using such compounds. In particular, compounds of the invention modulate the amount of Nav 1.7 protein on the cellular surface by modulating SUMOylation of CRMP2. Thus, compounds of the invention can be used to treat various clinical conditions associated with the presence and/or activation of Nav 1.7 protein on the cellular surface and/or SUMOylation of CRMP2.

Abstract: The present invention relates to substituted amide derivatives having dual pharmacological activity towards both the sigma (?) receptor, and the ?-opioid receptor, to processes of preparation of such compounds, to pharmaceutical compositions comprising them, and to their use in therapy, in particular for the treatment of pain.

Abstract: The invention relates to compounds and their use in the treatment of disease. Novel irreversible inhibitors of wild-type and mutant forms of EGFR, FGFR, ALK, ROS, JAK, BTK, BLK, ITK, TEC, and/or TXK and their use for the treatment of cell proliferation disorders are described.

Abstract: The invention relates to compounds of formula IB and methods for modulating one or more components of a kinase cascade using these compounds.

Abstract: An objective of the present invention is to obtain a stable crystal form of 5-chloro-6-(2-iminopyrrolidin-1-yl)methyl-2,4 (1H,3H)-pyrimidinedione hydrochloride. The present invention provides a crystal of 5-chloro-6-(2-iminopyrrolidin-1-yl)methyl-2,4 (1H,3H)-pyrimidinedione hydrochloride exhibiting characteristic peaks at angles of 11.6°, 17.2°, 17.8°, 23.3°, 27.1°, and 29.3° as a diffraction angle (2?±0.1°) in powder X-ray diffraction.

Abstract: The present invention relates to a therapeutic agent for chronic myelogenous leukemia with reduced drug-resistance and side-effects containing a 1,6-disubstituted indole compound.

Abstract: A compound exerts a strong analgesic effect against pain, in particular, neuropathic pain and/or fibromyalgia syndrome. A cyclic amine derivative represented by general formula or a pharmacologically acceptable salt thereof: A method of treating neuropathic pain includes administering a therapeutically effective amount of the cyclic amine derivative to a mammal. A method of treating fibromyalgia syndrome includes administering a therapeutically effective amount of the cyclic amine derivative to a mammal.

Abstract: The present disclosure provides substituted pyrimidine compounds of Formula (I), and the pharmaceutically acceptable salts, prodrugs, and solvates thereof, wherein A1, X, A2, W1, W2, W3, E, Z, and R4 are defined as set forth in the specification. The present disclosure is also directed to the use of compounds of Formula (I) to treat a disorder responsive to the blockade of sodium channels. Compounds of the present disclosure are especially useful for treating pain.

Abstract: The present invention relates to stable novel salt forms of N-(cyanomethyl)-4-(2-(4-morpholinophenylamino)pyrimidin-4-yl)benzamide that are suitable for the preparation of pharmaceutical formulations thereof, and their therapeutic use.

Abstract: The present invention relates to stable novel salt forms of N-(cyanomethyl)-4-(2-(4-morpholinophenylamino)pyrimidin-4-yl)benzamide that are suitable for the preparation of pharmaceutical formulations thereof, and their therapeutic use.