Abstract: Compounds having activity as inhibitors of G12C mutant KRAS protein are provided. The compounds have the following structure (I): or a pharmaceutically acceptable salt, tautomer, prodrug or stereoisomer thereof, wherein R1, R2a, R3a, R3b, R4a, R4b, G1, G2, L1, L2, m1, m2, A, B, W, X, Y, Z and E are as defined herein. Methods associated with preparation and use of such compounds, pharmaceutical compositions comprising such compounds and methods to modulate the activity of G12C mutant KRAS protein for treatment of disorders, such as cancer, are also provided.

Abstract: Derivatives of mDIVI-1 may be used to target and eliminate cancer stem cells. Disruption in the mitochondrial dynamics balance plays a role in cancer. Proteins involved in regulating mitochondrial dynamics represent potential targets for cancer treatment. Mitochondrial fission protein DRP1 is such a target. Derivatives of mDIVI-1 inhibit DRP1, and have demonstrated inhibition of tumorsphere forming capacity, migration and stemness-related signaling in breast cancer cells. These properties result from induction of mitochondrial oxidative stress and reduction of mitochondrial metabolism in the target cancer cells. The potency of an mDIVI-1 derivative may be dramatically increased through addition of at least one membrane-targeting signal and/or a mitochondria-targeting signal.

Abstract: The present invention relates compounds of Formula (A) as H3R antagonists, as well as their preparation and uses, and further relates pharmaceutical compositions comprising these compounds and their uses as modulators of Histamine 3 Receptor (H3R) functions. The present invention also relates to the uses of the compounds or pharmaceutical compositions in treating or preventing certain disorders and diseases which relate to H3R functions in humans.

Abstract: This invention is directed to the treatment of cancer, particularly ocular melanoma, with a dual inhibitor of MET and VEGF such as Compound 1.

Abstract: Disclosed are malate salts of N-(4-{[6,7-bis(methyloxy)-quinolin-4-yl]oxy}phenyl)-N?-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide, including a (L)-malate salt, a (D)-malate salt, a (DL) malate salt, and mixtures thereof; and crystalline and amorphous forms of the malate salts. Also disclosed are pharmaceutical compositions comprising at least one malate salts of N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N?-(4-fluorophenyl)-cyclopropane-1,1-dicarboxamide; and methods of treating cancer comprising administering at least one malate salt of N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N?-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide.

Abstract: A compound of formula I wherein A, X, Y, Z, R1 and R24 are described herein. The compounds are useful as inhibitors of potassium channel function and in the treatment and prevention of arrhythmia, IKur-associated disorders, and other disorders mediated by ion channel function.

Abstract: The present invention relates compounds of Formula (A) as H3R antagonists, as well as their preparation and uses, and further relates pharmaceutical compositions comprising these compounds and their uses as modulators of Histamine 3 Receptor (H3R) functions. The present invention also relates to the uses of the compounds or pharmaceutical compositions in treating or preventing certain disorders and diseases which relate to H3R functions in humans.

Abstract: This invention provides quinazoline derivatives represented by the structural formula: (I); wherein: R2 is hydrogen, NR?R?, C1-7 alkyl, arylC1-7 alkyl or C3-10 cycloalkyl; R4 is amino, C1-7 alkyl, C2-7 alkenyl, C3-10 cycloalkyl, C3-10 cycloalkenyl, aryl, heterocyclic, arylalkyl, heterocyclic-substituted C1-7 alkyl or C3-10 cycloalkyl-C1-7 alkyl; R5 is hydrogen or C1-7 alkyl, or R5 and R4 together with the nitrogen atom to which they are attached form a heterocyclic ring; Y is a single bond, C1-7 alkylene, C2-7 alkenylene or C2-7 alkynylene; R6 is halogen, heteroaryl or aryl; R? and R? are each independently hydrogen, C1-7 alkyl-carbonyl or C1-7 alkyl; provided that R4 is not phenyl substituted with morpholino when R2 is H and R5 is H, and provided that when NR4R5 is piperazinyl, said NR4R5 is either non-substituted or substituted with methyl or acetyl; a pharmaceutically acceptable addition salt, a stereoisomer, a mono- or a di-N-oxide, a solvate or a pro-drug thereof, for the treatment of viral infections.

Abstract: Methylene blue (MB) derivatives selectively detect F? by desilylation reaction to act as a fluorescent probe.

Abstract: Disclosed are a crystal of a maleate of a compound of formula (I), a preparation method for the crystal, a crystallization composition of same, a pharmaceutical composition of same, and uses thereof in preventing and treating a tumor.

Abstract: A method of treatment is disclosed herein. The method includes administering to a patient in need thereof a polymer implant device containing a biocompatible drug, or a plurality of nanoparticles or microparticles conjugated with the biocompatible drug, the biocompatible drug comprising one or more Rock inhibitors, one or more Wnt inhibitors, one or more integrin inhibitors, and/or one or more glycogen synthase kinase 3 (GSK-3) inhibitors, the patient having a medical condition selected from the group consisting of dry eye, glaucoma, retinal detachment, retinal degeneration, age-related macular degeneration, a cataract, uveitis, a corneal genetic disease, postoperative inflammation, immune-related inflammatory processes, diabetic retinopathy, a side effect occurring after cataract surgery, a side effect occurring after refractive surgery, and combinations thereof.

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

Abstract: The invention provides combinations comprising a MERTK inhibitor, or a pharmaceutically acceptable salt thereof, and an EGFR inhibitor and methods of use thereof, including methods of treating disorders such as cancer.

Abstract: Provided herein are bifunctional compounds that inhibit MALT1 and/or promote targeted ubiquitination for the degradation of MALT1. In particular, provided are compounds that can bind MALT1, a protein whose activity is responsible for constitutive NF-KB signaling in certain cancers (e.g., activated B-cell diffuse large B-cell lymphoma (ABC-DLBCL)), and can assist in its degradation by recruiting an E3 ubiquitin ligase (e.g., Cereblon, VHL), which can ubiquitinate MALT1, marking it for proteasome degradation. Also provided are pharmaceutical compositions comprising the bifunctional compounds, methods of treating cancer with the bifunctional compounds, methods of promoting the degradation of MALT1, and methods of binding E3 ubiquitin ligase activity in a subject by administering a compound or composition described herein.

Abstract: The present disclosure provides a method of treating a patient with refractory or resistant cancer by administering a therapeutically effective amount of a compound of formula (I), such as Varlitinib, or an enantiomer thereof or a pharmaceutically acceptable salt of any one of the same. Also provided is a compound of formula (I) for use in the treatment of resistant or refractory cancer and use of a compound of formula (I) for the manufacture of a medicament for the treatment of resistant or refractory cancer.

Abstract: The present invention relates to quinazolinones and related compounds which are inhibitors of PARP14 and are useful, for example, in the treatment of cancer and inflammatory diseases.

Abstract: The invention relates to quinazoline derivatives substituted by aniline which are represented by the below formula (I), pharmaceutical acceptable salts and stereoisomer thereof, wherein these groups of R1, R2, R3, R4, R5, R6, L and n have the meanings given in the specification. The invention also relates to preparation methods, pharmaceutical compositions, pharmaceutical preparation and the use for preparation of medicine of treating excessive hyperplasia and chronic obstructive pulmonary disease and uses for treating excessive hyperplasia and chronic obstructive pulmonary disease thereof.

Abstract: In one aspect the present disclosure provides a method of sensitizing a cancer patient to chemotherapy by administering a combination therapy comprising; a) a therapeutically effective amount of a compound of formula (I) an enantiomer thereof or a pharmaceutically acceptable salts of any one of the same, and b) a chemotherapeutic agent or a combination of chemotherapeutic agents.

Abstract: The present invention relates to compounds of formula I that function as inhibitors of PARG (Poly ADP-ribose glycohydrolase) enzyme activity wherein R1a, R1b, R1c, R1d, R1e, W, X1, X2, X3, X4, X5, X6, X7, c are each as defined herein. The present invention also relates to processes for the preparation of these compounds, to pharmaceutical compositions comprising them, and to their use in the treatment of proliferative disorders, such as cancer, as well as other diseases or conditions in which PARG activity is implicated.

Abstract: A compound of formula I wherein A, X, Y, Z, R1 and R24 are described herein. The compounds are useful as inhibitors of potassium channel function and in the treatment and prevention of arrhythmia, IKur-associated disorders, and other disorders mediated by ion channel function.

Abstract: The present disclosure relates to certain amine derivatives of fused bicyclic heterocycles that inhibit the amine reuptake function of the biogenic amine transporters, dopamine transporter (DAT), serotonin transporter (SERT) and norepinephrine transporter (NET). Compounds of the present disclosure are potent inhibitors of the reuptake of dopamine (DA), serotonin (5-hydroxytryptamine, 5-HT) and norepinephrine (NE) with full or partial maximal efficacy. The compounds with partial maximal efficacy in inhibiting reuptake of all three biogenic amines are herein referred to as partial triple uptake inhibitors (PTRIs). Compounds of the present disclosure are useful for treating depression, pain and substance abuse and relapse to substance abuse and addiction to substances such as cocaine, methamphetamine, nicotine and alcohol. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

Abstract: The present invention comprises compounds of Formula I wherein: R1, R2, R3, R4, R5, R7, R8, and are defined in the specification. The invention also comprises a method of treating or ameliorating a syndrome, disorder or disease, wherein the syndrome, disorder or disease is rheumatoid arthritis or psoriasis. The invention also comprises a method of modulating ROR?t activity in a mammal by administration of a therapeutically effective amount of at least one compound of Formula I.

Abstract: Compounds having activity as inhibitors of G12C mutant KRAS protein are provided. The compounds have the following structure (I): or a pharmaceutically acceptable salt, tautomer, prodrug or stereoisomer thereof, wherein R1, R2a, R3a, R3b, R4a, R4b, G1, G2, L1, L2, m1, m2, A, B, W, X, Y, Z and E are as defined herein. Methods associated with preparation and use of such compounds, pharmaceutical compositions comprising such compounds and methods to modulate the activity of G12C mutant KRAS protein for treatment of disorders, such as cancer, are also provided.

Abstract: Disclosed is a substituted pyrimidine compound having a structure as represented by formula PY. See the description for the definition of each substituent in the formula. The compound of the present invention provides broad-spectrum bactericidal, pesticidal, and acaricidal activities, provides great control effects against plant diseases such as cucumber downy mildew, corn rust, wheat powdery mildew, rice blast, and cucumber gray mold, specifically provides improved control effects against cucumber downy mildew, corn rust, wheat powdery mildew, and rice blast, provides great control effects against aphid, carmine spider mite, diamondback moth, and armyworm, and acquires great effects at a minimal dosage. The compound of the present invention also provides characteristics such as a simplified preparation method.

Abstract: The invention relates to quinazoline derivatives substituted by aniline which are represented by the below formula (I), pharmaceutical acceptable salts and stereoisomer thereof, wherein these groups of R1, R2, R3, R4, R5, R6, L and n have the meanings given in the specification. The invention also relates to preparation methods, pharmaceutical compositions, pharmaceutical preparation and the use for preparation of medicine of treating excessive hyperplasia and chronic obstructive pulmonary disease and uses for treating excessive hyperplasia and chronic obstructive pulmonary disease thereof.

Abstract: The present invention is directed to processes for making and compositions containing quinolines such as formula I or pharmaceutically acceptable salts thereof wherein: X1 is H, Br, CI, or X2 is H, Br, CI, or n1 is 1-2; and n2 is 1-2.

Abstract: This invention generally relates to compositions and methods for cancer treatment and, in particular, to compositions able to interact (e.g., bind to) with MUC1 growth factor receptor or its ligands, and methods for treating the same. The invention also relates to assays or use of such compositions for the treatment of patients susceptible to or exhibiting symptoms characteristic of cancer or tumorigenesis. Other compositions of the present invention useful for the treatment or prevention of cancer or tumorigenesis include homologs, analogs, derivatives, enantiomers or functional equivalents. The present compositions can also be packaged in kits in some cases.

Abstract: Quinazoline derivatives of formula (I): wherein A is 5-membered heteroaryl containing a nitrogen atom and one or two further nitrogen atoms; compositions containing them, processes for their preparation and their use in therapy.

Abstract: The present invention relates to AZD2171 maleate salt, to particular crystalline forms of AZD2171 maleate salt, to processes for their preparation, to pharmaceutical compositions containing them as active ingredient, to their use in the manufacture of medicaments for use in the production of antiangiogenic and/or vascular permeability reducing effects in warm-blooded animals such as humans, and to their use in methods for the treatment of disease states associated with angiogenesis and/or increased vascular permeability.

Abstract: A compound of formula I wherein A, X, Y, Z, R1 and R24 are described herein. The compounds are useful as inhibitors of potassium channel function and in the treatment and prevention of arrhythmia, IKur-associated disorders, and other disorders mediated by ion channel function.

Abstract: Disclosed herein are methods, compounds and compositions designed for ameliorating oxidative stress in cells. In particular, disclosed are viral vectors that express RNA interfering molecules for inhibiting expression or activity of Nox1 or RAC1. Depending on the location of administration, expression of inhibiting molecules can reduce oxidative stress in neurons associated with a particular neurodegenerative condition.

Abstract: Compounds of the formula I in which R1, R2, R3, X1, X2 and Y have the meanings indicated in Claim 1, are inhibitors of Tankyrase, and can be employed, inter alia, for the treatment of diseases such as cancer, cardiovascular diseases, central nervous system injury and different forms of inflammation.

Abstract: The subject invention concerns materials and methods for inhibiting the Akt/PKB pathway. In one embodiment, a compound of the invention inhibits kinase activity and/or phosphorylation levels of Akt proteins. The subject invention also concerns methods for inhibiting or killing a cancer cell or other cell in which expression of an Akt protein is elevated or constitutively active, comprising contacting the cell with an effective amount of a compound of formula I. The subject invention also concerns methods for treating cancer or a tumor in a person or animal comprising administering an effective amount of a compound of formula I to the person or animal.

Abstract: The present invention provides labeling and capture reagents that comprise phosphorothioate oligonucleotides (PS-ODN). The PS-ODN bind to all white blood cells (leukocytes) in an indiscriminative fashion and enable the labeling, capture, or concentration of leukocytes in a manner that preserves the antigenic integrity of the cells. Methods for the use of phosphorothioate oligonucleotides are provided.

Abstract: A compound for treating a protein kinase-related disease or disorder having a structure of formula (I) wherein G is a heteroaryl, heterocyclic or alkyne; X is N or CH; L1 is —N(R7)—, —O—, —C(S)—, —C(O)—, or —S—; L2 is —N(R8)— or —O—; R1 and R2 are independently hydrogen, halogen, hydroxyl, amino, cyano, nitro, carboxy, C1-C4 alkoxy, C1-C4 alkoxy C1-C4 alkoxy, N,N—(C1-C4 dialkyl)amino C1-C4 alkoxy, N—(C1-C4 alkyl)amino C1-C4 alkoxy, C1-C4 alkanoyl, C1-C4 alkanoyloxy, N—(C1-C4 alkyl)amino, N,N—(C1-C4 dialkyl)amino, C1-C4 alkanoyl amino, or heterocyclyl, wherein C1-C4 alkyl is optionally substituted with one or more substituents selected from fluorine and chlorine; R3, R4 and R5 are independently hydrogen, fluorine or chlorine; R6 is C1-C4 alkyl or aryl, which is optionally substituted with one or more substituents selected from halogen, hydroxyl, amino, cyano, nitro; or R6 and R8 form a 5-6 membered cyclyl or heterocyclyl.

Abstract: This invention is in the fields of cancer therapy. More particularly it concerns compounds which are useful agents for inhibiting cell proliferative disorders, especially those disorders characterized by over activity and/or inappropriate activity of a EGFR, including EGFR-related cancers, and methods for treating these disorders.

Abstract: The present invention relates to bicyclic heteroaryl cycloalkyldiamine derivatives, to processes for their production, to their use as SYK inhibitors and to pharmaceutical compositions comprising them.

Abstract: The present invention relates to a compound of formula (I), which has valuable pharmacological properties, particularly an inhibiting effect on signal transduction mediated by tyrosine kinases, processes for stereoselectively preparing these compounds, particularly pharmaceutical formulations suitable for inhalation and their use for the treatment of diseases, particularly tumoral diseases, benign prostatic hyperplasia and diseases of the lungs and airways.

Abstract: The invention provides 3-deuterium-enriched 3-(6-, 7-, or 8-substituted-4-oxoquinazolin-3(4H)-yl)-piperidine-2,6-diones, deuterated derivatives thereof, stereoisomers thereof, pharmaceutically acceptable salt forms thereof, and methods of treatment using the same.

Abstract: Solid forms comprising 3-(5-amino-2-methyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione, compositions comprising the solid forms, methods of making the solid forms and methods of their uses are disclosed.

Abstract: A compound of structural formula (I), wherein R is H or —PO3H or a pharmaceutically acceptable salt form thereof. The compounds are useful as inhibitors of potassium channel function and in the treatment and prevention of arrhythmia, IKur-associated disorders, and other disorders mediated by ion channel function.

Abstract: A series of new 6-piperazinyl-3,4-dihydroquinazolin-2(1H)-ones have been synthesized. The compounds are structurally related to adoprazine, a potential atypical antipsychotics bearing potent D2 receptor antagonist and 5-HT1A receptor agonist properties. Buchwald-Hartwig coupling of suitably modified aryl bromides with tert-butyl piperazine-1-carboxylate afforded the advanced intermediate piperazinyl-3,4-dihydroquinazolin-2(1H)-one. The reductive amination of the latter with appropriately designed biarylaldehydes accomplished the synthesis of these compounds.

Abstract: The present invention relates to the use of a series of quinazoline-derived compounds to produce a medicament for the treatment and/or prevention of neurological and/or neurodegenerative diseases, such as Parkinson's disease or Alzheimer's disease. The present invention also relates to a method for the treatment and/prevention of neurological and/neurodegenerative diseases comprising the administration of a therapeutically effective amount of said compounds.

Abstract: The invention relates to oligonucleotides including at least one FANA substituted nucleotide analog and a pyrimidine-purine dinucleotide. The invention also relates to pharmaceutical compositions and methods of use thereof.

Abstract: The invention provides quinazoline-7-ether derivatives, particularly 4-anilinyl-6-butenamido-quinazoline-7-ether derivatives that are inhibitors of the receptor protein tyrosine kinases (RTK). The compounds are useful in the treatment of diseases and disorders where RTK activity is implicated such as a hyperproliferative diseases (e.g., cancer). Also provided are methods of preparation of the quinazoline derivatives and methods of use as therapeutic agents alone or in a drug combination.

Abstract: This invention relates to methods for neuroprotection, promoting survival of motor neurons and the treatment of motor neuron diseases by preventing cell signaling through the classic prostaglandin D2 receptor DP1.

Abstract: The present invention relates to quinolinyloxyphenylsulfonamides and stereoisomeric forms, solvates, hydrates and/or pharmaceutically acceptable salts of these quinolinyloxyphenylsulfonamide compounds as well as pharmaceutical compositions containing at least one of these compounds together with at least one pharmaceutically acceptable carrier, excipient and/or diluent. Said quinolinyloxyphenylsulfonamides are useful for prophylaxsis, treatment and/or after-treatment of hyperproliferative disorders, such as cancer, tumors and particularly cancer metastases.

Abstract: Histone deacetylases inhibitors (HDACIs) and methods for treating cancer in a subject in need thereof are disclosed. The HDACIs comprise a compound of Formula X. or a pharmaceutically acceptable salt thereof. In one embodiment of the invention, R1 is ethyl; R2 is 2-phenylethyl; R3 is hydrogen; R4 is fluoro; R5 is (2E)-3-N-hydroxyamino-3-oxo-propenyl; and R6 is hydrogen, or a salt thereof. In another embodiment of the invention, R1 is ethyl; R2 is 2-phenylethyl; R3 is hydrogen; R4 is (2E)-3-N-hydroxyamino-3-oxo-propenyl; R5 is chloro or fluoro; and R6 is hydrogen.

Abstract: Compounds of formula (I) in which R3 is chosen from hydrogen, cyano, nitro, acetyl and C(?O)NH2, and Ar is optionally substituted monocyclic or bicyclic aryl or heteroaryl, are useful as antitumor agents.

Abstract: A series of new 6-piperazinyl-3,4-dihydroquinazolin-2(1H)-ones have been synthesized. The compounds are structurally related to adoprazine, a potential atypical antipsychotics bearing potent D2 receptor antagonist and 5-HT1A receptor agonist properties. Buchwald-Hartwig coupling of suitably modified aryl bromides with tert-butyl piperazine-1-carboxylate afforded the advanced intermediate piperazinyl-3,4-dihydroquinazolin-2(1H)-one. The reductive amination of the latter with appropriately designed biarylaldehydes accomplished the synthesis of these compounds.