Abstract: The present invention relates to Tetracyclic Heterocycle Compounds of Formula and pharmaceutically acceptable salts or prodrug thereof, wherein A, X, R1, R2, R3 and Ware as defined herein. The present invention also relates to compositions comprising at least one Tetracyclic Heterocycle Compound, and methods of using the Tetracyclic Heterocycle Compounds for treating or preventing HIV infection in a subject.

Abstract: Described are methods for disinfecting a physical or biological surface by contact with an antimicrobial formulation comprising a substituted tolan compound, the substitutions being, for example, one or more alkoxy, (e.g., methoxy) and hydroxy substituents at one or both phenyl rings of the tolan. The compounds and methods are -static and/or -cidal, depending on dose and suspected microbe. Suspected pathogenic microbes include Gram negative bacteria, such as P. aeruginosa and E. coli, Gram positive bacteria, such as S. aureus, including MRSA, and fungal pathogens, such as Candida genus and C. albicans. Also described are methods for inhibiting or disrupting biofilm formation of a microbe or microbes.

Abstract: Disclosed are methods for treating kidney disease including autosomal dominant polycystic kidney disease (ADPKD) in a subject, comprising the step of administering to the subject a composition comprising a therapeutically effective amount of ticagrelor or a derivative thereof, thereby treating ADPKD. Disclosed are methods of decreasing arginine vasopressin (AVP) production in a subject comprising the step of administering to the subject a composition comprising an effective amount of ticagrelor, thereby decreasing AVP production. Disclosed are methods for treating dilutional hyponatremia in a subject comprising the step of administering to the subject a composition comprising an effective amount of ticagrelor, thereby decreasing AVP production.

Abstract: Provided are a pharmaceutical composition of a substituted pyrazolo[1,5-a]pyrimidine macrocyclic compound and the use thereof. The pyrazolo[1,5-a]pyrimidine macrocyclic compound is a compound as shown in formula (Aa), or a pharmaceutically acceptable salt, a prodrug, a hydrate or a solvate, a crystal form, a stereoisomer or an isotopic variant thereof. The compound of the present invention is an inhibitor of the Trk kinase, and can be used for treating pain, cancers, inflammation, neurodegenerative diseases and certain infectious diseases.

Abstract: The invention relates to a compound of formula (I): A-B-D-E (I) or a pharmaceutically acceptable salt, solvate or polymorph thereof, including all tautomers and stereoisomers thereof, wherein: A is selected from monocyclic and bicyclic heteroaryl, which may independently substituted by alkyl or amino; B is selected from alkyl, heteroalkyl, alkyl-amino, aryl, heteroaryl, cycloalkyl, heterocyclyl and alkylene, wherein said groups may independently be substituted by alkyl; D is selected from aryl-amino, heteroaryl-amino, cycloalkyl-amino, heterocyclyl, heterocyclyl-amino, urea, thioamide, thiourea, sulfonamide, sulfoximine and sulfamoyl, wherein said aryl, heteroaryl, cycloalkyl and heterocyclyl groups may independently be substituted; and E is selected from aryl, heteroaryl, cycloalkyl, heterocyclyl, wherein said aryl, heteroaryl, cycloalkyl and heterocyclyl groups may independently be substituted. The compounds of formula (I) are inhibitors of glutaminyl cyclase (QC, EC 2.3.2.5).

Abstract: The present disclosure pertains to compositions and methods for the treatment and/or prevention of one or more of obesity, diabetes, metabolic syndrome, Alzheimer's disease, Chronic Fatigue Syndrome (CFS), aging, fibromyalgia, dyslipidemia, hypercholesterolemia, dyslipidemia, Parkinson's disease, migraines, Traumatic Brain Injury (TBI), Attention Deficit Disorder (ADD)/Attention Deficit Hyperactivity Disorder (ADHD), Cancer, Cardiovascular Disease (CVD)/Coronary Artery Disease (CAD), Chronic Pain, neuralgia, depression, amyotrophic lateral sclerosis (ALS), and epilepsy, Insufficient Cellular Energy (ICE) and mitochondrial dysfunction. The present disclosure also pertains to methods for increasing mental and/or physical performance levels and/or decreasing exertion during exercise in a subject by the administration of C5 ketones.

Abstract: Provided are compounds that can act as a modulator of a farnesoid X receptor (FXR) and that can be useful in the treatment of diseases and/or disorders associated with the FXR such as bile acid related disorders, metabolic syndrome, type-2-diabetes, hyperlipidemia, hypertriglyceridemia, primary biliary cirrhosis (PBC), fatty liver disease, nonalcoholic steatohepatitis (NASH), inflammatory autoimmune diseases, Crohn's disease, multiple sclerosis, atherosclerosis, kidney disorders (including chronic kidney disease), hepatic and colon cancers, and other disorders. The compounds are in the class of sulfinic acid compounds and can be an enantiomer, stereoisomer, tautomer, solvate, hydrate, prodrug, metabolite, or pharmaceutically acceptable salt thereof. Compositions including such compounds are also provided along with methods for preparing compounds of the present invention and their use.

Abstract: The disclosure generally relates to substituted purine analogs that are dual CLK2/CDK1 inhibitors or more potent and specific CLK inhibitors to target CLK2 and CDK1 kinases. These compounds may be useful in the treatment of germ-line mutations of the spliceosome leading to the development of cancers and other human disease. 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 discloses compounds of Formula (I), and pharmaceutically acceptable salts, thereof: which inhibit coronavirus replication activity. The invention further relates to pharmaceutical compositions comprising a compound of Formula (I) or a pharmaceutically acceptable salt thereof, and methods of treating or preventing a coronavirus infection in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound of Formula (I) or a pharmaceutically acceptable salt thereof.

Abstract: The present disclosure relates to novel forms of fedratinib dihydrochloride (diHCl) and processes for the preparation of the various forms. The present disclosure also relates to pharmaceutical compositions comprising the novel forms of fedratinib dihydrochloride and methods for treating disease using the forms.

Abstract: Described herein are compounds of Formula (I) and tautomers and pharmaceutical salts thereof, compositions and formulations containing such compounds, and methods of using and making such compounds.

Abstract: The present disclosure relates to substituted aryl and heteroaryl compounds, pharmaceutical compositions comprising such compounds, and use of such compounds in methods of treatment or in medicaments for treatment of inflammatory diseases and certain neurological disorders that are related to inflammatory signaling processes, including but not limited to misfolded proteins.

Abstract: Provided herein are methods for treating a cholecystokinin (CCK) receptor-expressing cancerous tumor in a subject. The methods comprising administering to the subject an effective amount of a CCK receptor inhibitor and an effective amount of an immune checkpoint inhibitor, wherein the CCK receptor inhibitor inhibits one or more CCK receptors selected from the group consisting of a CCK-A receptor, a CCK-B receptor and a CCK-C receptor, and wherein the immune checkpoint inhibitor is a programmed cell death protein 1 (PD1) inhibitor or a cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) inhibitor.

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, isotopic form or stereoisomer thereof, wherein A is a five-membered heteroaryl comprising 1 or 2 non-adjacent heteroatoms, inclusive of X and Y; W, X, Y, Z, L, L1, E, R1, R2b R2c and the dotted circle are as defined herein. Methods associated with preparation and use of such compounds, pharmaceutical compositions comprising such compounds and compounds for use in methods to modulate the activity of G12C mutant KRAS protein for treatment of disorders, such as cancer, are also provided. Preferred compounds are e.g. 1-(3-(6-(3-hydroxynaphthalen-1-yl)benzofuran-2-yl)azetidin-1yl)prop-2-en-1-one derivatives and related compounds such as e.g. the corresponding derivatives with e.g. a benzoimidazole, indole, benzooxazole, imidazopyridine or imidazole core structure, substituted on ring A by e.g.

Abstract: Herein are described the preparation of a series of synthetic rocaglates, amidino- and amino-rocaglates, which display inhibition of protein translation and tumor cell proliferation (in vitro and in vivo). The methods described herein allow the preparation of libraries of modified rocaglates. This chemical modification of the rocaglate scaffold changes the C8b-hydroxyl of the natural product series to a more optimal hydrogen bond donor/acceptor.

Abstract: Provided herein are myeloid cell leukemia 1 protein (Mcl-1) inhibitors, methods of their preparation, related pharmaceutical compositions, and methods of using the same. For example, provided herein are compounds of Formula I, or a stereoisomer thereof; and pharmaceutically acceptable salts thereof and pharmaceutical compositions containing the compounds. The compounds and compositions provided herein may be used, for example, in the treatment of diseases or conditions, such as cancer.

Abstract: The present invention is directed to, in part, fused heteroaryl compounds and compositions useful for preventing and/or treating a disease or condition relating to aberrant function of a voltage-gated, sodium ion channel, for example, abnormal late/persistent sodium current. For example, such compounds include those having the structure: or pharmaceutically acceptable salts thereof. Methods of treating a disease or condition relating to aberrant function of a sodium ion channel, including Dravet syndrome or epilepsy, using such compounds are also provided herein.

Abstract: The disclosure provides for compounds of the general structure: and methods of using and compositions comprising the compounds for treating infections, cancer and neoplastic diseases and disorders.

Abstract: The present invention provides, inter alia, a process for producing a compound of Formula (I): wherein A1, R1, R2, R3, R4, R5 and R6 are as defined herein. The present invention further provides intermediate compounds utilised in said process, and methods for producing said intermediate compounds.

Abstract: The present invention relates to a manufacturing process and intermediates for preparing a crystalline or non-crystalline form of N-((1S,3S)-3-(methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)cyclobutyl)propane-1-sulfonamide. The present invention also relates to salt forms and pharmaceutical compositions comprising the crystalline form, and to methods for use of the compound prepared from a crystalline form in the treatment of various diseases.