Abstract: Disclosed are compounds of Formula 1 and pharmaceutically acceptable salts thereof, wherein L, R4, R5, R8, R10, R11, X1, X2, X3, X9, X12, and Z are defined in the specification. This disclosure also relates to materials and methods for preparing compounds of Formula 1, to pharmaceutical compositions which contain them, and to their use for treating diseases, disorders, and conditions associated with GPR6.

Abstract: The present invention provides a compound of Formula (I): or an enantiomer, an enantiomeric mixture, or a pharmaceutically acceptable salt thereof; wherein the variables are as defined herein. The present invention further provides pharmaceutical compositions comprising such compounds; and methods of using such compounds for treating a disease or condition mediated by nuclear SET domain-containing protein 2 (NSD2).

Abstract: Provided are 2-(piperidin-1-yl)pyrimidin-4(3H)-ones or pharmaceutically acceptable salts thereof, each characterized by having a 1,8-diazaspiro[4.5]deca-3-ene, 1-oxa-8-azaspiro[4.5]deca-3-ene, 2,8-diazaspiro[4.5]deca-3-ene, 2-oxa-8-azaspiro[4.5]deca-3-ene, 2,9-diazaspiro[5.5]undeca-3-ene, 1-oxa-9-azaspiro[5.5]undeca-3-ene, 1,9-diazaspiro[5.5]undeca-4-ene, or 3,9-diazaspiro[5.

Abstract: Disclosed are new intermediates for the synthesis of Linagliptin and of its salts and a process for its preparation involving said intermediates.

Abstract: Certain embodiments are directed to methods of treating autoimmune disorders by administering P2 purnergic receptor antagonist and/or adenosine receptor antagonists. The P2 purnergic receptor antagonist being chemical analogs of adenosine receptor antagonist 8-Ethoxy-9-ethyl-9H-purin-6-amine. The adenosine receptor antagonists being chemical analogs of the non-hydrolysable ATP analog adenosine 5?[?-thio]triphosphate (ATP?S). Certain embodiments are directed to the use of the chemical analogs to modulate IL-17 activity.

Abstract: Provided herein are methods of treating focal segmental glomerulosclerosis, said methods include administering to a subject in need thereof a therapeutically effective amount of a CCR2 antagonist. In some embodiments, the CCR2 antagonist is used in monotherapy. In some embodiments, the CCR2 antagonist is used in combination therapy. In some embodiments, the additional therapeutic agent is a RAAS blocker and/or an endothelin receptor inhibitor. The CCR2 antagonist may have the structure of formula (I).

Abstract: A compound of the Formula I and optionally a pharmaceutically acceptable salt thereof is provided: Formula I, wherein, R is one selected from the group consisting of H and CH3; n is an integer 4 when X is —CH2— and Ar is 1,4-phenyl, or n is an integer ranging from 1 to 4 when X is —CH2— and Ar is either 2?-fluoro-1,4-phenyl or 2,5-thienyl, or n is an integer ranging from 1 to 4 when X is one selected from the group consisting of O, S, —NH—, —NHCHO—, —NHCOCH3—, and —NHCOCF3— and Ar is one selected from the group consisting of (a) 1,4-phenyl, (b) 2?-fluoro-1,4-phenyl, and (c) 2,5-thienyl, or n is an integer 3 when X is —CH2—, R is CH3 and Ar is 1,4-phenyl.

Abstract: The present invention relates to novel purines of general formula A processes for their preparation, pharmaceutical compositions containing them and their use in therapy, particularly in the treatment or prevention of conditions having an association with NR2B negative allosteric modulating properties.

Abstract: The present disclosure relates to compounds, compositions and methods for treating cancer, including compounds that are capable of penetrating the blood brain barrier to modulate the activity of EGFR tyrosine kinase. The disclosure further relates to methods of treating cancer in the brain, including glioblastoma and other EGFR mediated cancers. The disclosure further relates to methods of treating cancers such as glioblastoma and other EGFR mediated cancers that have been determined to have altered glucose metabolism in the presence of inhibitors. The present disclosure also provides methods of administering to a subject a glucose metabolism inhibitor and a cytoplasmic p53 stabilizer.

Abstract: This invention provides for prodrug Compounds I, pharmaceutical compositions thereof, and their use in treating HIV infection. wherein: X is C or N with the proviso that when X is N, R1 does not exist; W is C or N with the proviso that when W is N, R2 does not exist; V is C; E is hydrogen or a pharmaceutically acceptable salt thereof; and Y is selected from the group consisting of Also, this invention provides for intermediate Compounds II useful in making prodrug Compounds I. wherein: L and M are independently selected from the group consisting of C1-C6 alkyl, phenyl, benzyl, trialkylsilyl, -2,2,2-trichloroethoxy and 2-trimethylsilylethoxy.

Abstract: Disclosed herein are processes for preparing 2-[(3R)-3-[4-amino-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methyl-4-[4-(oxetan-3-yl)piperazin-1-yl]pent-2-enenitrile free base (compound (I)), salts of compound (I) and solid state form of said salts. Also disclosed herein are pharmaceutical compositions comprising such salts and solid state form thereof and methods of treating cancer, autoimmune, and inflammatory diseases using compound (I) or a pharmaceutically acceptable salt thereof.

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.