Abstract: This invention relates to novel compounds that are substituted xanthine derivatives and pharmaceutically acceptable salts thereof. For example, this invention relates to novel substituted xanthine derivatives that are derivatives of pentoxifylline. This invention also provides compositions comprising one or more compounds of this invention and a carrier and the use of the disclosed compounds and compositions in methods of treating diseases and conditions for which pentoxifylline and related compounds are beneficial.

Abstract: The invention provides compounds that inhibit the degradation of Wee1. The compounds of the present invention are generally N-((1H-benzo[d]imidazol-2-yl)methyl)-9H-purin-6-amines. Compounds of the invention can be used for treatment of malconditions in patients for which inhibition of Wee1 is medically indicated, for example cancer, Alzheimer's, neurological disorders, psychiatric disorders, or inflammation-related disorders.

Abstract: The present invention relates to 3-hydroxypyrrolidine compounds of the general formula (I) which are inhibitors of 5?-methylthioadenosine phosphorylase or 5?-methylthioadenosine nucleosidase. The invention also relates to the use of these compounds in the treatment of diseases or conditions in which it is desirable to inhibit 5?-methylthioadenosine phosphorylase or 5?-methylthioadenosine nucleosidase including cancer, and to pharmaceutical compositions containing the compounds.

Abstract: Provided herein are methods for treating or preventing a solid tumor, non-Hodgkin lymphoma or multiple myeloma in a patient, comprising administering an effective amount of a TOR kinase inhibitor to a patient having a solid tumor, non-Hodgkin lymphoma or multiple myeloma.

Abstract: The present invention provides novel PI3-Kinase antagonists having the formula: and methods of use thereof.

Abstract: The present invention is concerned with novel antifungal 5,6-dihydro-4H-pyrrolo-[1,2-a][1,4]benzodiazepines and 6H-pyrrolo[1,2-a][1,4]benzodiazepines substituted with heterocyclic derivatives of Formula (I) wherein R1, R2, R3, R4 and Het have the meaning defined in the claims. The compounds according to the present invention are active mainly against dermatophytes and systemic fungal infections. The invention further relates to processes for preparing such novel compounds, pharmaceutical compositions comprising said compounds as an active ingredient as well as the use of said compounds as a medicament.

Abstract: The present invention relates to new piperidine inhibitors of Janus kinase 3 activity, pharmaceutical compositions thereof, and methods of use thereof.

Abstract: Novel crystalline forms of 3-(imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methyi-N-{4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyljbenzamide free base and 3-(imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methyi-N-{4-[(4-methyl piperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}benzamide mono hydrochloride, pharmaceutical compositions thereof and methods of their preparation and use are disclosed herein. The instant application is directed to novel crystalline forms of 3-(imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methyi-N-{4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl}phenyl}benzamide and 3-(imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methyi-N-{4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}benzamide mono hydrochloride, compositions comprising such crystalline forms, and to methods of their preparation and use.

Abstract: The present invention relates to pyrimidine derivatives capable of inhibiting one or more protein kinases. Further aspects relate to pharmaceutical compositions comprising the pyrimidine derivatives and the use thereof in the treatment of proliferative disorders.

Abstract: The invention relates to substituted benzoxazoles and to processes for their preparation and to their use for preparing medicaments for the treatment and/or prophylaxis of diseases, in particular of cardiovascular disorders, preferably of thrombotic or thromboembolic disorders.

Abstract: Novel synthetic approaches to make 3-(imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methyl-N-[4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]benzamide, intermediates and pharmaceutically acceptable salts thereof are provided.

Abstract: This invention relates to compounds of Formula I having the following general structure: Z1—Y1—(CH2)n1—R—(CH2)n2—Y2—Z2 wherein R represents a fused bicyclic or spirocyclic aliphatic diamine and pharmaceutically acceptable salts thereof which are inhibitors of the Renal Outer Medullary Potassium (ROMK) channel (Kir1.1). The compounds are useful as diuretics and natriuretics and therefore are useful for the therapy and prophylaxis of disorders resulting from excessive salt and water retention, including cardiovascular diseases such as hypertension and chronic and acute heart failure.

Abstract: A cationic polymer is disclosed, represented by: A) wherein “P1” and “P2” represent portions of the cationic polymer to which the first functional group shown in A is bonded, or B) wherein “P” represents the remainder of the cationic polymer to which the second functional group shown in B is bonded, or the cationic polymer may comprise one or more of the first functional groups as shown in A and/or one or more of the second functional groups as shown in B where X represents an anion, typically chlorine. The cationic polymers are useful as textile softeners and for enhancing substantivity and durability of active compounds co-deposited onto textiles with the cationic polymers. Also provided is a method for forming said cationic polymer, a textile treatment composition and a textile treated with said textile treatment composition.

Abstract: Compounds of Formula I: and pharmaceutically acceptable salts thereof, wherein ring A, ring B, W, m, D, R2, R2a, R3, R3a, and Z are as defined herein, are inhibitors of Trk kinases and are useful in the treatment of pain, cancer, inflammation, neurodegenerative diseases and certain infectious diseases.

Abstract: A method of providing a patient with controlled release of ketone-containing opioid using a prodrug capable, upon enzymatic activation and intramolecular cyclization, of releasing the ketone-containing opioid is disclosed. The disclosure also provides such prodrug compounds and pharmaceutical compositions comprising such compounds. Such pharmaceutical compositions can optionally include an enzyme inhibitor that interacts with the enzyme(s) to mediate the enzymatically-controlled release of the ketone-containing opioid from the prodrug so as to modify enzymatic cleavage of the prodrug. Also included are methods to use such compounds and pharmaceutical compositions.

Abstract: The present invention provides a fused ring compound containing furan or a pharmaceutically acceptable salt thereof, a method for preparing same, a pharmaceutical composition comprising same, and a use thereof. The fused ring compound containing furan or a pharmaceutically acceptable salt thereof inhibits the activity of phosphatidylinositol 3-kinase (PI3K) and can therefore be used in a pharmaceutical composition for treating and preventing respiratory diseases, inflammatory diseases, proliferative diseases, cardiovascular diseases, or central nervous system diseases which occur due to the over-activation of PI3K.

Abstract: The present invention relates to 4-Pyridone Compounds of Formula (I); and pharmaceutically acceptable salts and prodrugs thereof, wherein A, R1, R2, and R3 are as defined herein. The present invention also relates to compositions comprising at least one 4-Pyridone Compound, and methods of using the 4-Pyridone Compounds for treating or preventing HIV infection in a subject or the clinical manifestations thereof.

Abstract: Anilide derivatives of the natural trioxane artemisinin were prepared and evaluated for antimalarial efficacy in Plasmodium berghei-infected mice. Selected anilides derivatives administered orally as one single-digit dose combined with mefloquine hydrochloride were completely curative, i.e., all 5 of the mice in the particular treatment group had no detectable parasitemia on day 30 post infection, gained as much weight by day 30 post infection as the control mice (no infection), and behaved normally.

Abstract: In one aspect, the invention relates to substituted 5-aminothieno[2,3-c]pyridazine-6 -carboxamide analogs, derivatives thereof, and related compounds, which are useful as positive allosteric modulators of the muscarinic acetylcholine receptor M4 (mAChR M4); synthesis methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating neurological and psychiatric disorders associated with muscarinic acetylcholine receptor dysfunction using the compounds and compositions. 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: Disclosed herein are compounds, and pharmaceutical compositions that include such compounds, for preventing or treating hearing loss. The compounds and pharmaceutical compositions described herein prevent or treat hair cell death. In addition, the compounds and pharmaceutical compositions described herein protect against kidney damage in an individual receiving an aminoglycoside antibiotic. Methods of using the compounds, alone or in combination with other therapeutic agents, are also disclosed.

Abstract: The present invention relates to compounds useful as inhibitors of bromodomain-containing proteins. The invention also provides pharmaceutically acceptable compositions comprising compounds of the present invention and methods of using said compositions in the treatment of various disorders.

Abstract: Provided is a compound having an AMPA receptor function enhancing action, and useful as a prophylactic or therapeutic drug for depression, schizophrenia, Alzheimer's disease, attention deficit hyperactivity disorder (ADHD) and the like. The compound represented by formula (I): wherein each symbol is as defined in the DESCRIPTION, or a salt thereof has an AMPA receptor function enhancing action, and is useful as a prophylactic or therapeutic drug for depression, schizophrenia, Alzheimer's disease or attention deficit hyperactivity disorder (ADHD) and the like.

Abstract: Compounds are provided having a structure according to Formula (I): wherein A1, A2, A3, Y, R1, R2, R3, R4, R5, R6, m, n and p are defined herein. Further provided are pharmaceutical compositions including the compounds provided and methods of making and using the compounds and compositions as provided, e.g., in the treatment and prevention of various disorders, such as Alzheimer's disease.

Abstract: The invention provides novel compounds having the general formula (I) wherein R1, R2, Y and W are as described herein, compositions including the compounds and methods of using the compounds.

Abstract: Azaindazole compounds for treating various diseases and pathologies are disclosed. More particularly, the present invention concerns the use of an azaindazole compound or analogs thereof, in the treatment of disorders characterized by the activation of Wnt pathway signaling (e.g., cancer, abnormal cellular proliferation, angiogenesis, fibrotic disorders, bone or cartilage diseases, and osteoarthritis), the modulation of cellular events mediated by Wnt pathway signaling, as well as genetic diseases and neurological conditions/disorders/diseases due to mutations or dysregulation of the Wnt pathway and/or of one or more of Wnt signaling components. Also provided are methods for treating Wnt-related disease states.

Abstract: The present invention is to provide highly solid state emissive fluorophores of the formula 1 and 2 useful for the solid state lighting. The formula 1 and 2 have good solid state emission in blue and green region respectively. The zinc complexes of formula 1A and 2A have yellow and red emission respectively in solid state. The present invention also provide high solid state emissive assay of formula 1 and 2 to convert UV light into visible light by coating the color tunable materials on the 365-nm emitting solid state LED. The present invention further provides carbazole end-capped bipyridine for screening of metal salts with different counterions in solutions. The discrimination of the various metal salts can be monitored by noting the fluorescence change in solution. The zinc salts with different counterions have different emission color in solution. The present invention also develop a new two photon active fluorescent Zn2+ specific probe for detecting Zn2+ in cellular environments.

Abstract: This invention provides, among other things, novel compounds useful for treating protozoal infections, pharmaceutical compositions containing such compounds, as well as combinations of these compounds with at least one additional therapeutically effective agent.

Abstract: This invention provides novel compounds of the following formula and pharmaceutical compositions containing such compounds.

Abstract: A process for the removal of acids from reaction mixtures, comprising at least one product of value which is sparingly soluble in water, by at least one unpolar amine as an auxiliary base, which includes: a) reacting the auxiliary base with the acid with formation of a salt; b) reacting the salt formed in step a) with a further base which accepts the acid with liberation of the auxiliary base and combines with the acid to be accepted from the auxiliary base to form a salt which is very readily soluble in water; c) extraction of the mixture obtained in step b) with water or an aqueous medium, wherein the salt of the further base dissolves in the aqueous phase and the product of value, or the solution of the product of value, in a suitable solvent and the auxiliary base form at least one separate nonaqueous phase; and d) removal by distillation of at least part of any solvent present from the at least one nonaqueous phase obtained in step c), to form two nonmiscible liquid phases.

Abstract: A method for producing a compound represented by General Formula (1), the method including: reacting a compound represented by General Formula (3) and a compound represented by General Formula (4): where R1 and R2 each represent aliphatic group which may have substituent, or aromatic group which may have substituent (with the proviso that R1 and R2 are different groups), R3 represents aromatic group which may have substituent, and R4 represents aliphatic group which may have substituent, or aromatic group which may have substituent, where R1 and R2 each represent aliphatic group which may have substituent, or aromatic group which may have substituent (with the proviso that R1 and R2 are different groups), and R3 represents aromatic group which may have substituent, where R4 represents aliphatic group which may have substituent, or aromatic group which may have substituent.

Abstract: Disclosed herein, inter alia, are acyclic nucleotide analogs and methods of using an acyclic nucleotide analog for treating and/or ameliorating a papillomavirus infection.

Abstract: Provided are a novel phosphinine oxide derivative and a preparation method thereof, and more specifically, the phosphinine oxide derivative includes an oxaphosphinine oxide derivative and an azaphosphinine oxide derivative. The phosphinine oxide derivative according to the present invention may have a pharmacological activity and a physiological activity, and may be used as a basic framework of a natural product and may be used for development of new drug and synthesis of various medical supplies. In addition, according to the preparation method of the phosphinine oxide derivative according to the present invention, various phosphinine oxide derivatives with a high yield may be prepared by a simple synthesis process using an intramolecular annulation between a phosphinic derivative and an alkyne derivative in the presence of a rhodium (Rh) catalyst or a ruthenium (Ru) catalyst and an oxidant.

Abstract: Biomass feedstocks (e.g., plant biomass, animal biomass, and municipal waste biomass) are processed to produce useful products, such as fuels. For example, systems are described that can use feedstock materials, such as cellulosic and/or lignocellulosic materials and/or starchy materials, to produce a product or intermediate, e.g., energy, a food, a fuel, or a material.

Abstract: The invention provides an alginate oligosaccharide and its derivatives with the degree of polymerization ranging from 2 to 22. The alginate oligosaccharide is composed of ?-D-mannuronic acid linked by 1,4 glycosidic bonds. The derivatives with the reduced terminal in position 1 of carboxyl radical can be prepared by oxidative degradation. The invention also provides a process for preparing the alginate oligosaccharide and its derivatives, which includes the procedure that an alginate solution is reacted for 2 to 6 h in an autoclave at pH 2˜6 and the temperature of 100˜120° C., and adjusted pH to 7 after the reaction is stopped, after which the resultant oligosaccharide is oxidized in the presence of an oxidant to obtain an oxidative product. The alginate oligosaccharide and its derivatives of the invention can be used in the manufacture of a medicament for the prophylaxis and treatment of AD and diabetes.

Abstract: The invention provides a compound effective as an antitumor active agent or vaccine adjuvant and an intermediate useful for the synthesis of the compound, as well as production methods thereof, and a medicament containing the novel compound. The compound is a carbamate glycolipid represented by the formula (I) wherein each symbol is as defined herein. The invention also provides a dendritic cell pulsed with the glycolipid.

Abstract: Provided herein are conjugates comprising a protein and an oligosaccharide of one of Formulae I-VI. Also provided herein are pharmaceutical compositions comprising such conjugates. Further provided herein are methods of treating a lysosomal storage disorder in a mammal by administration of an oligosaccharide-glycoprotein conjugate.

Abstract: The current invention provides methods (e.g., large-scale processes) for the production of nucleotide sugars, which are modified with a polymeric modifying group, such as poly(alkylene oxide) moieties (e.g., poly(ethylene glycol) or poly(propylene glycol)) moieties. A typical process of the invention includes anion exchange chromatography followed by an ultrafiltration procedure, such as tangential flow filtration. The process of the invention provides modified nucleotide sugars in unexpectedly high purity and high overall yields.

Abstract: The present invention provides fluorinated 5-aza-2?-deoxycytidine compounds, such as 2?,2?-difluoro-5-aza-2?-deoxycytidine, compositions that include the compounds, methods for making the compounds, and methods for inhibiting DNA methyltransferase, treating solid tumors, and treating hematologic cancers by administering the compounds.

Abstract: Compounds having methyltransferase inhibitory activity are disclosed. The compounds have the structure and are useful in the treatment of cancer and similar diseases associated with inappropriate methyltransferase activity.

Abstract: The present invention relates to the compounds of the formulae (I) and (I-1) and the process for preparing the same, uses of the compounds for the treatment of diseases associated with platelet aggregation and in the manufacture of a medicament for the treatment of diseases associated with platelet aggregation, and relates to a pharmaceutical composition and a pharmaceutical formulation containing the compounds, wherein the definitions of R1, R2, R3 and R2a in the formulae are the same as those in the description.

Abstract: Chemical entities that are novel compounds, pharmaceutical compositions and methods of treatment of cancer are described.

Abstract: The present invention relates to the field of radiopharmaceuticals for in vivo imaging, in particular to a method of labelling a biological targeting molecule with a radioisotope. The method of the invention is particularly suitable for use with an automated synthesizer apparatus. Also provided are precursors in sterile form, as well as cassettes comprising such precursors useful in the method.

Abstract: The present invention provides novel conformationally-defined macrocyclic compounds that have been demonstrated to be selective modulators of the ghrelin receptor (growth hormone secretagogue receptor, GHS-R1a and subtypes, isoforms and variants thereof). Methods of synthesizing the novel compounds are also described herein. These compounds are useful as agonists of the ghrelin receptor and as medicaments for treatment and prevention of a range of medical conditions including, but not limited to, metabolic and/or endocrine disorders, gastrointestinal disorders, cardiovascular disorders, obesity and obesity-associated disorders, central nervous system disorders, genetic disorders, hyperproliferative disorders and inflammatory disorders.

Abstract: The present invention relates to novel macrocyclic compounds and methods of treating a hepatitis C infection in a subject in need of such therapy with said macrocyclic compounds. The present invention further relates to pharmaceutical compositions comprising the compounds of the present invention, or pharmaceutically acceptable salts, esters, or prodrugs thereof, in combination with a pharmaceutically acceptable carrier or excipient.

Abstract: Use of synthetic thiol-containing peptides as highly effective therapeutic and protective agents is described, in clinical and research applications where lifespan and/or viability and functioning of cells is compromised at least partially due to depletion of reduced glutathione, or where viability and functioning of cells can be improved by elevating reduced glutathione levels. More specifically, compositions and methods for treating blood disorders associated with glutathione dysregulation utilizing short thiol-containing peptides selected from the group consisting of Cys-Lys-Met-Cys (SEQ ID NO: 1), Cys-Met-Lys-Cys (SEQ ID NO: 2) and Cys-?-Ala-His-Cys (SEQ ID NO: 3) are described. Further described are compositions and methods for preserving biological samples using the peptides.

Abstract: The present invention provides polypeptide inhibitors of HSP27 kinase, compositions thereof, and methods for using such polypeptides and compositions for various therapeutic uses.

Abstract: The present invention provides novel peptidomimetic macrocycles and methods for their preparation and use, as well as amino acid analogs and macrocycle-forming linkers, and kits useful in their production. Macrocycles of the invention include triazole moieties that crosslink amino acid side chains. The cross links can stabilize a secondary structure of a peptidomimetic macrocycle, such as an ?-helix.

Abstract: The present invention relates to inhibitors of protein-protein interactions (PPI). Specifically, the present invention relates to a structural informatics approach to designing peptidomimetic macrocycles containing an amino acid “warhead” for ligand-directed covalent modification of cysteine and lysine-containing proteins for the treatment of diseases such as cancer. Further included is the targeting of components of the BCL2 signaling pathway, specifically BCL2-A1 and MCL-1.

Abstract: Disclosed herein are novel analogs of cyclosporin, pharmaceutical compositions containing them, and methods for their use in the treatment of dry eye and other conditions.

Abstract: The invention relates to a method or process for solution phase chemical manufacture of depsipeptides of the formula I, wherein the symbols have the meaning defined in the description, to new intermediates and their manufacture, as well as related invention embodiments.