Abstract: The present disclosure provides methods for treating Alzheimer's disease (AD) comprising administering clomipramine or a pharmaceutically acceptable salt thereof. The administration of clomipramine increases the levels of TAp73 and decreases the levels of proliferating cell nuclear antigen (PCNA) and cleaved caspase-3 in the AD patients. The methods of the present disclosure reduce the neurodegeneration and improve the cognitive and functional decline in AD patients.

Abstract: The present invention provides crystalline solids of 6?-((6-aminopyrimidin-4-yl)amino)-8?-methyl-2?H-spiro[cyclohexane-1,3?-imidazo[1,5-a]pyridine]-1?,5?-dione: The crystalline compounds of the present application are inhibitors of Mnk and finds utility in any number of therapeutic applications, including but not limited to treatment of inflammation and various cancers.

Abstract: The present invention provides compounds, e.g., compounds of Formula (I) and pharmaceutically acceptable salts, solvates, hydrates, tautomers, stereoisomers, isotopically labeled derivatives, and compositions thereof. Also provided are implantable elements (e.g., devices and materials) comprising the same, as well as methods of use thereof, e.g., for treating or preventing a disease, disorder, or condition.

Abstract: The present invention relates to compounds of formula I: and pharmaceutically acceptable salts thereof, pharmaceutical compositions comprising the compounds of formula I or their pharmaceutically acceptable salts, and methods of using said compounds, salts and compositions in the treatment of various disorders associated with CRM1 activity.

Abstract: The application relates to a compound having Formula X: which modulates the activity of HER2 and/or a mutant thereof, and/or EGFR and/or a mutant thereof, a pharmaceutical composition comprising the compound, and a method of treating or preventing a disease in which HER2 and/or a mutant thereof, and/or EGFR and/or a mutant thereof, plays a role.

Abstract: Biotransformation of an aromatase inhibitor, testolactone (1), yielded four metabolites, 7?-hydroxy-3-oxo-13,17-seco-5?-androsta-1-eno-17,13?-lactone (2), 3?,11?-dihydroxy-13,17-seco-5?-androsta-17,13?-lactone (3), 4?,5?-epoxy-3?-hydroxy-13,17-secoandrosta-1-eno-17,13?-lactone (4), and 4?,5?-epoxy-3?-hydroxy-13,17-secoandrosta-1-eno-17,13?-lactone (5). Aromatase (estrogen synthase) involves in the synthesis of estrogen, and promotes the growth of breast cancerous cells. It is a key target for the discovery of chemotherapeutic agents against ER+(estrogen-positive) breast-cancers. Metabolites 2 (IC50=8.63±0.402 nM), and 3 (IC50=9.23±1.31 nM) were identified as potent inhibitors against human aromatase enzyme, in comparison to 1 (IC50=0.716±0.031 ?M), and the standard aromatase inhibiting drug, exemestane (IC50=0.232±0.031 ?M). Derivatives 4 (IC50=10.37±0.50 ?M) and 5 (IC50=0.82±0.059 ?M) also showed a good inhibition against aromatase enzyme.

Abstract: Embodiments of the present invention provide a pharmaceutical intervention in the neonatal pig that inhibits and delays development and activation of the HPG axis, growth of the boar testis and inhibits testicular production of testosterone and androstenone, which prevents the development of aggressive behavior in the maturing boars and the presence of boar taint in the meat. The invention comprises treatment with a combination of an androgen and an estrogen in the newborn male piglet using extended drug delivery methods, with a defined duration of no more than 12 weeks, for the purpose of inhibiting the production of testosterone and androstenone and the accumulation of the boar taint-inducing molecules androstenone and skatole in the fat.

Abstract: The invention provides substituted pyrazolo[1,5-a]pyrimidine and related organic compounds, compositions containing such compounds, medical kits, and methods for using such compounds and compositions to treat medical disorders, e.g., Gaucher disease, Parkinson's disease, Lewy body disease, dementia, or multiple system atrophy, in a patient. Exemplary substituted pyrazolo[1,5-a]pyrimidine compounds described herein include 5,7-dimethyl-N-phenylpyrazolo[1,5-a]pyrimidine-3-carboxamide compounds and variants thereof.

Abstract: Compounds and compositions are disclosed in which a NAMPT Drug Unit is conjugated to a targeting Ligand Unit through quaternization by a Linker Unit from which a NAMPT inhibitor compound or derivative thereof is released at the targeted site of action. Methods for treating diseases characterized by the targeted abnormal cells, such as those of cancer or an autoimmune disease, using the compounds and compositions of the invention are also disclosed.

Abstract: Disclosed are compounds of Formula (I) to (VIII): or a stereoisomer, tautomer, pharmaceutically acceptable salt, solvate or prodrug thereof, wherein R3 is a tricyclic heteroaryl group substituted with R3a and zero to 2 R3b; and Ri, R2, R3a, R3b, R4, and n are defined herein. Also disclosed are methods of using such compounds as PAR4 inhibitors, and pharmaceutical compositions comprising such compounds. These compounds are useful in inhibiting or preventing platelet aggregation, and are useful for the treatment of a thromboembolic disorder or the primary prophylaxis of a thromboembolic disorder.

Abstract: A compound of Formula (I), or a pharmaceutically acceptable salt thereof, is provided that has been shown to be useful for treating a PRC2-mediated disease or disorder: wherein R1, R2, R3, R4, R5, and n are as defined herein.

Abstract: An 8-(4-nitroxybenzylideneamino)naphthalene-1,3-disulfonic acid compound, its synthesis, and its use as an antioxidant agent.

Abstract: Disclosed herein are kinase inhibitory compounds, such as a receptor-interacting protein-1 (RIP1) kinase inhibitor compounds, as well as pharmaceutical compositions and combinations comprising such inhibitory compounds. The disclosed compounds, pharmaceutical compositions, and/or combinations may be used to inhibit a RIP1 kinase in vivo or ex vivo, and also may treat or prevent a kinase-associated disease or condition, particularly a RIP1-associated disease or condition.

Abstract: Provided herein are compounds of Formula (I) and Formula (II) and stereoisomers, tautomers, and pharmaceutically acceptable salts or solvates thereof. Also provided are pharmaceutical compositions comprising these compounds and methods of treating a disease, disorder, or condition by using the compounds and pharmaceutical compositions.

Abstract: The present application provides tricyclic heteroaryl compounds that activate the STING pathway to produce interferons, which are useful in the treatment of various diseases including infectious diseases and cancer.

Abstract: The present invention relates to a method for preventing transmission of influenza, wherein said method comprises administering an effective amount of a compound to a patient having an influenza virus infection, herein referred to as “index patient”, wherein the compound has one of the formulae (I) and (II), or its pharmaceutically acceptable salt. The compound to be used in the present invention reduces infectivity of the influenza virus of the index patient, and therefore, reduces the risk of the index patient to trigger an influenza epidemic or an influenza pandemic as compared to a control patient.

Abstract: This application relates to chemical compounds which may act as inhibitors of, or which may otherwise modulate the activity of, PCSK9, or a pharmaceutically acceptable salt, solvate, prodrug or polymorph thereof, and to compositions and formulations comprising such compounds, and methods of using and making such compounds. Compounds include compounds of Formula (I): wherein A, D and Q are described herein.

Abstract: Provided herein, inter alia, are methods and compounds for modulating Interleukin-2-inducible T-cell kinase.

Abstract: Novel compounds having D3 receptor antagonistic activity are provided. A compound represented by formula (I): wherein ring A is a heterocycle, X1 is each independently CR4aR4b, X2 is each independently CR4cR4d, Y1 and Y2 are each independently a carbon atom or a nitrogen atom, L is —N(R6)—C(?O)— or the like, W is cyclyl or the like, R2 and R3 are each independently substituted or unsubstituted alkyl or the like, R1a, R1b, R4a to R4d, and R6 are each independently hydrogen atoms or the like, p is 1 or 2, q is an integer of 1 to 3, n is an integer of 1 to 4, s is an integer of 0 to 4, or a pharmaceutically acceptable salt thereof.

Abstract: Disclosed herein are compounds, compositions and methods for the treatment of neurological, psychiatric disorders which are characterized by a fundamental disruption of social behaviour, and substance use disorders. In particular, disclosed herein are compounds of Formula (I), or salts or prodrugs thereof. Methods of treating or preventing neurological, psychiatric disorders and substance use disorders, using compounds of Formula (I), or salts and prodrugs are also disclosed.