Abstract: The novel benzimidazole hexahydrofuro[3,2-B]furan derivatives of the present invention are activators of AMP-protein kinase and may be useful in the treatment, prevention and suppression of diseases mediated by the AMPK-activated protein kinase. The compounds of the present invention may be useful in the treatment of Type 2 diabetes, hyperglycemia, metabolic syndrome, obesity, hypercholesterolemia, and hypertension.

Abstract: The present invention relates to a combination comprising at least one compound selected from the group consisting of an ?-adrenergic antagonist, an anthelmintic agent, an antifungal agent, an antimalarial agent, an antineoplastic agent, an antipsychotic agent, an antioxidant, a vasodilator, a vitamin, or a pharmaceutically acceptable derivative thereof; and an antimicrobial compound.

Abstract: The present invention provides methods and compositions comprising compounds useful for stimulating neurogenesis. The methods and compositions comprising compounds are also useful for inhibiting neuronal degeneration. Thus, the present invention can be used in the treatment of diseases and conditions characterized by neuronal loss and reduced neurogenesis including Alzheimer's disease, stroke, traumatic brain injury, and depression. This invention could also be used for research products including single agents or mixtures of agents to promote, proliferate, differentiate, or maintain neurons from stem or progenitor cells.

Abstract: Provided in the present invention are a 2-arylbenzofuran-7-formamide compound as shown in general formula I or a pharmacologically or physiologically acceptable salt thereof, a preparation method thereof and use thereof in preparing anti-tumour drugs, wherein R1 and R2 are each independently hydrogen, straight or branched chained C1-C4 alkyl, C3-C4 cycloalkyl or saturated 5- or 6-membered heterocyclyl containing oxygen or nitrogen; or R1 and R2 together with N form an unsubstituted or substituted saturated 5- or 6-membered heterocyclyl containing at least one heteroatom, wherein the heteroatom is O, N and S, the substituent is a methyl on N; R3 is a hydrogen atom or a chlorine atom; R4 is a hydrogen atom or a fluorine atom; X is CH, CF or N; and Y is CH, CF or N.

Abstract: Novel compounds described herein are activators of AMP-protein kinase and may be useful in the treatment, prevention and suppression of diseases mediated by the AMPKactivated protein kinase. The compounds of the present invention may be useful in the treatment of Type 2 diabetes, hyperglycemia, metabolic syndrome, obesity, hypercholesterolemia, and hypertension.

Abstract: The present invention is directed to novel processes for the preparation of histamine H3 receptor modulators, in the treatment of for example, cognitive disorders, sleep disorders and/or psychiatric disorders.

Abstract: This invention demonstrates the formation of a novel polarized membrane lipid raft signaling module in neurons, in response to several diverse neurotoxic stimuli. This polarization occurs well before neurons commit to die, and is an early mechanism in death signaling. The formation of this signaling module is dependent on cholesterol for its formation and provides a mechanistic explanation for the protective effects of cholesterol depleting drugs in several non-neural models of cell death. As such, the formation of the signaling module lends itself as a novel screen for the identification of new drugs and therapeutics which would retard its formation and protect against neuronal injury and death.

Abstract: The present disclosure relates generally to thienopyrimidine and thienopyridine compounds and methods of use thereof. In particular embodiments, the present disclosure provides compositions comprising thienopyrimidine and thienopyridine compounds of Formula 2: and methods of use to inhibit the interaction of menin with MLL1, MLL2 and MLL-fusion oncoproteins.

Abstract: Fused pyrimidine compounds as kinase inhibitors, such as multi-kinase inhibitors, are provided. Fused pyrimidine compounds as IGF-IR inhibitors are provided. Fused pyrimidine compounds that are inhibitors of Trk receptors (e.g., Trk A, Trk B and Trk C) are provided also. The compounds may be used in a method of treating cancer. Pharmaceutical compositions containing a fused pyrimidine compound and a pharmaceutically acceptable carrier are also provided, as are kits containing a fused pyrimidine compound or salt thereof and instructions for use, e.g., in a method of treating cancer.

Abstract: (R)-2-Arylpropionamide compounds of formula (I), pharmaceutical preparations of the compounds and a process for making the compounds are described. The 2-Arylpropionamides of the invention are useful in the prevention and treatment of tissue damage due to the exacerbated recruitment of polymorphonuclear leukocytes and monocytes at inflammatory sites. In particular, the invention relates to the R enantiomers of omega-aminoalkylamides of 2-aryl propionic acids, of formula (I), for use as inhibitors of chemotaxis of neutrophils and monocytes induced by the C5a fraction of complement and by other chemotactic proteins whose biological activity is associated with activation of a 7-TD receptor. Selected compounds of formula (I) are dual inhibitors of both the C5a-induced chemotaxis of neutrophils and monocytes and the IL-8-induced chemotaxis of polymorphonuclear leukocytes.

Abstract: Dosage forms for oral administration of a PDE 4 inhibitor whose solubility is slight are described. They contain PVP as binder.

Abstract: Disclosed herein are methods for identifying compounds for the treatment of viral infection, including RNA viral infection and uses of the compounds as pharmaceutical compositions. The identified compounds modulate the RIG-I pathway in vertebrate cells.

Abstract: The present document describes novel molecules having protein tyrosine kinase inhibitory activity, and methods of synthesizing and using such compounds. More specifically, the present document describes compound of Formula (A): (Formula (A)) or a pharmaceutically acceptable salt, hydrate or solvate thereof, and methods of synthesizing and using such compounds.

Abstract: The present invention discloses triazine compounds of Formula II and a process to synthesize these compounds. Particularly, the invention provides one pot method to synthesize triazines nucleus, wherein the method comprises amination followed by using Leuckart reaction conditions of pyrrole/indole-2-carboxylates of Formula I to obtain corresponding triazine compounds of Formula II.

Abstract: The present invention relates to novel 5,6-disubstituted oxindole derivatives and pharmaceutically acceptable salts thereof, and pharmaceutical compositions comprising such derivatives, and to the use of such derivatives for the manufacture of a medicament, and methods of treating disorders in a subject in need thereof, such as vasopressin-dependent disorders, using 5,6-disubstituted oxindole derivatives.

Abstract: The invention relates to the use of compounds of formula (I) in the treatment of mammalian target of rapamycin (mTOR) kinase dependent diseases, methods of use of said compounds in the treatment of said diseases in a warm-blooded animal, especially a human, pharmaceutical preparations comprising said compounds for the treatment of said diseases and said compounds for use in the treatment of said diseases.

Abstract: The present invention provides uses of a glucokinase activator in combination with metformin. Uses include treating type 2 diabetes, lowering blood glucose, improving insulin sensitivity, enhancing phosphorylation of glucose, and improving the therapeutic effectiveness of metformin. The invention also provides pharmaceutical compositions that comprise a GK activator and metformin. The invention also provides a salt formed between metformin and a GK activator.

Abstract: The present invention relates to novel chemical compounds formula (I) (C)n—B-(A)m-B—(C)n (I) wherein m is 0 or 1, and n is independently 0, 1, 2 or 3, A, each B and each C are independently selected from phenylene and five- and six-membered heteroaromatic rings, and for a terminal ring B or C also from bicyclic heteroaromatic fused rings having seven to ten ring members, wherein the bond between at least two of the rings A to C may be replaced by a carbonyl group (—CO—), wherein at least two of the rings A to C are substituted with one or two groups R, and wherein each ring A to C further optionally is substituted with one or two groups R1. The compounds are useful in therapy, especially therapy of a mammal suffering from a disease involving misfolded or aggregated forms of proteins.

Abstract: Disclosed are compounds that are antagonists of the CXCR4 receptor.

Abstract: The present invention relates to a compound of Formula I: or a pharmaceutically acceptable salt thereof, wherein the symbols are as defined in the specification; a pharmaceutical composition comprising the same; and a method for treating or preventing autoimmunity disease using the same.

Abstract: The present invention provides compounds that function as modulators of aldehyde dehydrogenase activity; and pharmaceutical compositions comprising the compounds. The present invention provides therapeutic methods involving administering a subject compound, or a subject pharmaceutical composition.

Abstract: The present invention provides a method of treating acute heart failure by administering a compound of the formula: or a pharmaceutically acceptable salt thereof.

Abstract: A method for treating a disease characterized by excessive lipofuscin accumulation in the retina in mammals afflicted therewith, comprising administering to the mammal an effective amount of a non-retinoid antagonist compound or a pharmaceutically acceptable salt thereof.

Abstract: Biocidal branched quaternary ammonium polymers are made by condensing a difunctional halide with a trifunctional tertiary amine and optionally with a difunctional amine. The branched quaternary ammonium polymers have 2-dimensional conformation that provides better coverage over the surfaces of microorganisms and enhances efficacy as biocides as compared to most commercially available linear (one-dimensional) quaternary ammonium polymers. The bulkier 2-dimensional conformation of this invention limits the uptake, accumulation and release of these branched polymers to and from contact lenses. Therefore, these branched quaternary ammonium polymers can reduce the cytotoxicity, enhance compatibility and suitable for ophthalmic use. The highly branched polymers can be prepared with minimum or no difunctional tertiary amines. The lightly branched polymers can be prepared with of a minimum ratio of trifunctional tertiary amines/difunctional tertiary amines.

Abstract: A combination of a CDK4/6 inhibitor and a P3Kinase inhibitor for the treatment of cancer.

Abstract: Disclosed are selective phosphodiesterase inhibitor compounds shown in formula (I) or (II) for treating Erectile Dysfunction, the pharmaceutically acceptable salts and configurational isomers thereof. In the formula, the substituents R1, R2, R3, R4 and R5 are defined as in the specification. Also disclosed are methods for preparing same, and a medical composition comprising compounds of formula (I) or (II), and the use of these compounds for preparing a drug treating or preventing male Erectile Dysfunction.

Abstract: The present invention provides compounds of Formula (I): or stereoisomers, pharmaceutically acceptable salts thereof, wherein all of the variables are as defined herein. These compounds are inhibitors of factor XIa and/or plasma kallikrein which may be used as medicaments.

Abstract: Provided herein are 2,5-disubstituted arylsulfonamide CCR3 antagonists, e.g., compounds of Formula I, and pharmaceutical compositions thereof: Also provided herein are methods of their use for treating, preventing, or ameliorating one or more symptoms of a CCR3-mediated disorder, disease, or condition.

Abstract: The present disclosure is directed to compositions and methods which utilize the tetracycline scaffold, preferably the scaffold of tetracycline or minocycline, and which significantly lack antibiotic activity. The compounds have neuroprotective attributes without interfering with the drugs capacity to pass through the blood brain barrier. These compounds have neuroprotective activity because of their inhibition of neuronal cell cycle progression. The compounds are characterized in part by a fifth ring joining positions 9 and 10.

Abstract: Provided are compounds of Formula I: or a pharmaceutically acceptable salt thereof, wherein R2, R4, R5, R6, R7, R8, R9, X, Z1, Z2, Z3, Z4 and m are as defined herein. Also provided is a pharmaceutically acceptable composition comprising a compound of Formula I, or a pharmaceutically acceptable salt thereof. Also provided are methods of using a compound of Formula I, or a pharmaceutically acceptable salt thereof.

Abstract: The present invention relates to novel benzene-carboxamide compounds having a structure that corresponds to the general formula (I), and also to their method of synthesis and to their use in pharmaceutical compositions intended for use in human or veterinary medicine or else to their use in cosmetic compositions.

Abstract: The present invention is directed to processes for preparing a diazepane compound which is an antagonist of orexin receptors, and which is useful in the treatment or prevention of neurological and psychiatric disorders and diseases in which orexin receptors are involved. The present invention is further directed to crystalline forms of this diazepane compound and pharmaceutical compositions thereof.

Abstract: The present invention relates to (1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenyl derivatives having the general formula (I) to pharmaceutical compositions comprising the same and to the use of these (1,1,1,3,3,3-hexafluoro-2-hydroxy-propan-2-yl)phenyl derivatives in the treatment of atherosclerosis.

Abstract: Provided are picolinamide and pyrimidine-4-carboxamide compounds, a method for preparing the same, a pharmaceutical composition containing the same, and a medical use using the compound as an agent for preventing, regulating, and treating diseases related to regulation of glucocorticoids by using selective inhibitory activity of the compound for an 11?-HSD1 enzyme. The picolinamide and pyrimidine-4-carboxamide compounds of the present invention are selective inhibitors of human-derived 11?-HSD1 enzymes, and are useful in an agent for preventing, regulating, and treating diseases related to glucocorticoid regulation in which human-derived 11?-HSD1 enzymes are involved, for example, metabolic syndromes such as, type 1 and type 2 diabetes, diabetes later complications, latent autoimmune diabetes adult (LADA), insulin tolerance syndromes, obesity, impaired glucose tolerance (IGT), impaired fasting glucose (IFG), damaged glucose tolerance, dyslipidemia, atherosclerosis, hypertension, etc.

Abstract: The invention relates to plasminogen activator-1 (PAI-1) inhibitor compounds and uses thereof in the treatment of any disease or condition associated with elevated PAI-1. The invention includes, but is not limited to, the use of such compounds to modulate lipid metabolism and treat conditions associated with elevated PAI-1, cholesterol, or lipid levels.

Abstract: The present invention provides compounds of general formula A, useful as potential anti-tubercular agents against Mycobacterium tuberculosis H37Rv, and drug-resistant Mycobacterium tuberculosis and a process for the preparation thereof wherein, n=5-12 n1=0,1 R=CF3 or Cl.

Abstract: The present disclosure provides pharmaceutical compositions, pharmaceutical preparations and methods for increasing activity of a mutant cystic fibrosis transmembrane conductance regulator protein (mutant-CFTR). The pharmaceutical compositions, pharmaceutical preparations and methods are useful for the study and treatment of disorders associated with mutant-CFTR, such as cystic fibrosis. The pharmaceutical compositions and pharmaceutical preparations may include one or more cyanoquinoline-containing compounds of the embodiments, or an analog or derivative thereof.

Abstract: The present invention relates to shelf-stable liquid formulations of palonosetron for reducing chemotherapy and radiotherapy induced emesis with palonosetron. The formulations are particularly useful in the preparation of intravenous and oral liquid medicaments.

Abstract: The invention provides certain substituted pyridines of the Formula (I) or pharmaceutically acceptable salts thereof, wherein R1, R2, R3, R4, Rcy, Cy, and t are as defined herein. The invention also provides pharmaceutical compositions comprising such compounds, and methods of using the compounds for treating diseases or conditions mediated by Spleen Tyrosine Kinase (Syk) kinase.

Abstract: A method of inhibiting the growth of cancer cells is disclosed in which cancer cells that contain an enhanced amount relative to non-cancerous cells of one or more of phosphorylated mTOR, Akt1, ERK2 and serine2152-phosphorylated filamin A are contacted with an FLNA-binding effective amount of a compound or a pharmaceutically acceptable salt thereof that binds to the pentapeptide of filamin A (FLNA) of SEQ ID NO: 1 and exhibits at least about 60 percent of the FITC-labeled naloxone binding amount when present at a 10 ?M concentration and using unlabeled naloxone as the control inhibitor at the same concentration. A compound that binds to the FLNA pentapeptide preferably also contains at least four of the six pharmacophores of FIGS. 19-24.

Abstract: Methods and agents for reducing a level of an acetylated Tau polypeptide in a cell are provided. Methods for treating a tauopathy in an individual are also provided. Also provided is a method for diagnosing a cognitive impairment disorder in an individual. Methods for identifying an agent suitable for treating a tauopathy are also provided.

Abstract: The present invention provides compounds of the formula: which are useful as inhibitors of PHD and pharmaceutical compositions thereof.

Abstract: The invention relates to novel compounds of Formula I: wherein A1, A2, A3, A4, A5, A6, R2, R4, R5, R6, R7, R8 and subscripts m and n each has the meaning as described herein. Compounds of Formula I and pharmaceutical compositions thereof are useful in the treatment of disease and disorders in which undesired or over-activation of NF-kB signaling is observed.

Abstract: This disclosure is directed to pyrido[4,3-b]indole and pyrido[3,4-b]indole derivatives. Pharmaceutical compositions comprising the compounds are also provided, as are methods of using the compounds in a variety of therapeutic applications, including the treatment of a cognitive disorder, psychotic disorder, neurotransmitter-mediated disorder and/or a neuronal disorder.

Abstract: The present invention relates to substituted thienopyrimidine compounds of general formula (I) as described and defined herein, to methods of preparing said compounds, to intermediate compounds useful for preparing said compounds, to pharmaceutical compositions and combinations comprising said compounds and to the use of said compounds for manufacturing a pharmaceutical composition for the treatment or prophylaxis of a disease, in particular of a hyper-proliferative and/or angiogenesis disorder, as a sole agent or in combination with other active ingredients.

Abstract: Methods are provided herein for treating cardiac arrhythmias, such as for treating an arrhythmia syndrome, for example Brugada syndrome, in a subject. In some embodiments, the methods include selecting a subject with Brugada syndrome and administering to the subject an effective amount of an agent that increases the expression or activity of SIRT1 in the subject. In some embodiments, the agent increases Nav1.5 activation. In some embodiments, the agent increases the expression or activity of SRIT1 and increases Nav1.5 activation.

Abstract: Provided herein are compounds useful for the treatment of HBV infection in a subject in need thereof, pharmaceutical compositions thereof, and methods of inhibiting, suppressing, or preventing HBV infection in the subject.

Abstract: A method for preventing or treating a disease selected from the group consisting of visceral pain, inflammatory pain, osteoarthritis pain, neuropathic pain, and fibromyalgia in a subject in need thereof, comprising administering to said subject an effective amount of the compound of the following formula (I) or a salt thereof: wherein R1, R2, R3, R4, R5, X and n are as described herein.

Abstract: The present invention relates to pyrazolo[3,4-b]pyridine compounds of the formula I, in which R1, R2, R3, R4, R5 and R6 are defined as indicated below. The compounds of the formula I are kinase inhibitors, and are useful for the treatment of diseases associated with diabetes and diabetic complications, such as, diabetic nephropathy, diabetic neuropathy and diabetic retinopathy, for example. The invention furthermore relates to the use of compounds of the formula I, in particular as active ingredients in pharmaceuticals, and pharmaceutical compositions comprising them.

Abstract: Substituted indazole derivatives of formula (I) and pharmaceutically acceptable salts thereof, as defined in the specification; the compounds of the invention may be useful in therapy in the treatment of diseases associated with a deregulated protein kinase activity, like cancer.