Abstract: The invention relates to 1,7-diazacarbazole compounds of Formula (I), (I-a) and (I-b) which are useful as kinase inhibitors, more specifically useful as checkpoint kinase 1 (chk1) inhibitors, thus useful as cancer therapeutics. The invention also relates to compositions, more specifically pharmaceutical compositions comprising these compounds and methods of using the same to treat various forms of cancer and hyperproliferative disorders, as well as methods of using the compounds for in vitro, in situ, and in vivo diagnosis or treatment of mammalian cells, or associated pathological conditions.

Abstract: The present invention relates to novel compounds and pharmaceutical compositions thereof which may be useful in the treatment and/or prevention of various conditions. The present invention also provides methods of preparing such compounds and compositions, and methods of using the same.

Abstract: Certain TRPV1-modulating imidazolo-, oxazolo-, and thiazolopyrimdine compounds are described. The compounds may be used in pharmaceutical compositions and methods for treating disease states, disorders, and conditions mediated by TRPV1 activity, such as pain, arthritis, itch, cough, asthma, or inflammatory bowel disease.

Abstract: An improved process for the preparation of Pralatrexate which is less hazardous. The invention further relates to novel intermediates and process thereof useful for the preparation of Pralatrexate. The present invention also relates to a substantially pure Pralatrexate and a process for obtaining the same in high yield.

Abstract: A method of screening a compound having a hypoglycemic effect (hereinafter referred to as “hypoglycemic compound”), a remedy for diabetes which contains a compound having a novel function mechanism, etc. More specifically speaking, a method of screening a hypoglycemic compound capable of binding to the ? subunit of a trimeric GTP-binding protein, a remedy for diabetes comprising a hypoglycemic compound, which is characterized by being capable of binding to the ? subunit of a trimeric GTP-binding protein, as the active ingredient, etc.

Abstract: Disclosed are a pyrrolo[2,1-f][1,2,4]triazine derivative of Formula (I) and use thereof for treating tumors. The compound has remarkable antiproliferative activity for a variety of human tumor cell lines, and is useful for treating cancers, especially solid tumors such as gastric cancer, lung cancer, liver cancer, breast cancer, colon cancer, prostatic cancer, and oral cancer.

Abstract: The present invention is directed to compounds that modulate the bioactivity of an orexin receptor such as OX1 or OX2, or both; to pharmaceutical compositions and combinations comprising a compound of the invention; to methods of treatment of malconditions in patients wherein modulation of an orexin receptor is medically indicated; and to methods of preparation of compounds of the invention.

Abstract: This invention relates to novel Pyrrolo[3,2-d]pyrimidine-2,4(3H,5H)-dione derivatives of Formula (I): and their use as TRPC5 modulators, pharmaceutical compositions containing the same, and methods of using the same as agents for the treatment of TRPC5 receptor mediated disorders or conditions. R1, R2, R3 R4 and R5 have meanings given in the description.

Abstract: This application provides compounds of the general formula (I) and/or a salt thereof, where X, R1 and R2 are as defined herein. Compositions and therapeutic uses are also described.

Abstract: The invention relates to novel 3,6,9-triazatricyclo[7.3.1.1]tetradecane-4,8,12-trione derivatives of general formula (1), which act as allosteric AMPA receptor modulators, and to drugs based thereon which can be used for treating Alzheimer's, Parkinson's and other neurodegenerative diseases.

Abstract: Crystalline, anhydrous hydrochloride salts of 4,5?-epoxy-3,14-dihydroxy-17-methylmorphinan-6-one (oxymorphone) are disclosed and three polymorphic forms of these salts are reported. The invention further relates to a method for the production of such salts, a pharmaceutical composition comprising an effective amount of such a salt and such a salt as a medicament and for the treatment and/or prevention of pain.

Abstract: The present invention provides an aromatic ring compound having a melanin-concentrating hormone receptor antagonistic action and useful as an agent for the prophylaxis or treatment of obesity and the like. The present invention relates to a compound represented by the formula wherein each symbol as defined in the specification, or a salt thereof.

Abstract: The present invention makes available, inter alia, methods and reagents for modulating smoothened-dependent pathway activation. In certain embodiments, the subject methods can be used to counteract the phenotypic effects of unwanted activation of a hedgehog pathway, such as resulting from hedgehog gain-of-function, ptc loss-of-function or smoothened gain-of-function mutations.

Abstract: It relates to spirocyclic compounds of formula (I), or pharmaceutically or veterinary acceptable salts thereof, or any stereoisomers either of the compounds of formula (I) or of their pharmaceutically or veterinary acceptable salts, wherein A and B form a spirocyclic ring system wherein the spiro atom connecting A and B is a carbon atom and wherein A is a known 3- to 8-membered carbocyclic or heterocyclic monocyclic ring or a known 6- to 18-membered carbocyclic or heterocyclic polycyclic ring system; B is a known 4- to 7-membered carbocyclic or heterocyclic monocyclic ring; C is phenyl or a known 5- to 6-membered heteroaromatic ring; and R1-R7 are as defined herein. It also relates to a process for their preparation, as well as to the intermediates used in this process; to pharmaceutical or veterinary compositions containing them, and to their use in medicine, in particular as antifibrinolytic and antihemorragic agents.

Abstract: The present invention provides a compound useful as an agent for the prophylaxis or treatment of neurodegenerative disease and the like, or a salt thereof. The present invention relates to a compound represented by the formula (I) wherein each symbol is as defined in the specification, or a salt thereof.

Abstract: The present disclosure provides processes for the preparation of a compound of formula I: which is useful as an antiviral agent. The disclosure also provides compounds and processes for the preparation of the compounds that are synthetic intermediates to the compound of formula I.

Abstract: There are disclosed novel 5-substituted 7-amino-[1,3]thiazolo[4,5-d]pyrimidine derivatives of formula (I) wherein R1, R2, R3, R4 and R5 are as defined in the specification, and pharmaceutically acceptable salts thereof, together with processes for their preparation, pharmaceutical compositions comprising them and their use in therapy. The compounds of formula (I) are CX3CR1 receptor antagonists and are thereby particularly useful in the treatment or prophylaxis of neurodegenerative disorders, demyelinating disease, cardio- and cerebrovascular atherosclerotic disorders, peripheral artery disease, rheumatoid arthritis, pulmonary diseases such as COPD, asthma or pain.

Abstract: The present invention relates to the use of compounds which are capable of attenuating skin irritation when they are applied to the skin. Skin irritation can be caused, inter alia, by ingredients of cosmetic or pharmaceutical compositions and/or environmental irritants. In particular, the present invention relates to compounds having the property of antagonizing the activation of the transient receptor potential (TRP) ankyrin 1 (TRPA1) ion channel and the use of said compounds as soothing agents. Such compounds can be used in many fields, particularly in personal-care products, cosmetics, textile and packaging products, pharmaceutical compositions, medical devices, and foodstuffs. The present invention further relates to products and/or pharmaceutical compositions containing said compounds. The present invention also relates to the use of the compounds described herein for the modulation of the taste of a food product.

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. The exemplary compounds have the following formula: wherein X is selected from the group consisting of substituted phenyl, substituted or unsubstituted heteroaryl and unsubstituted cycloalkyl; R3a is selected from the group consisting of H, unsubstituted C1 or C2 or C3 or C4 or C5 or C6 alkyl and unsubstituted C3 or C4 or C5 or C6 cycloalkyl; R3b is selected from the group consisting of H, unsubstituted C1 or C2 or C3 or C4 or C5 or C6 alkyl and unsubstituted C3 or C4 or C5 or C6 cycloalkyl; with the proviso that R3a and R3b, along with the atom to which they are attached, are optionally joined to form a 3 or 4 or 5 or 6 membered ring, with the proviso that R3a and R3b cannot both be H, or a salt thereof.

Abstract: Compounds according to Formula I are potent inhibitors of Arginase I and II activity: where R1, R2, R3, R4, D, W, X, Y, and Z are defined in the specification. The invention also provides pharmaceutical compositions of the compounds and methods of their use in treating or preventing a disease or a condition associated with arginase activity.

Abstract: The present invention relates to an alpha-alkoxysilane-terminated prepolymer preparable by reaction of at least one polyether polyol, of a polyisocyanate and of an alpha-alkoxysilane having at least one isocyanate-reactive group, said polyether polyol having a weight average of 500 to 7000 g/mol and having ethylene oxide and propylene oxide units, the proportion of ethylene oxide units being up to 50% by weight based on the polyether polyol. The invention further provides a process for preparing an inventive alpha-alkoxysilane-terminated prepolymer, a composition, a multicomponent system and a spray can comprising an inventive alpha-alkoxysilane-terminated prepolymer, and also a moulding obtainable by polymerization from an inventive alpha-alkoxysilane-terminated prepolymer.

Abstract: This invention relates to hydrolysable silanes useful in the modification of elastomers, and as coupling agents for diene elastomer compositions containing a filler. In particular the invention relates to novel hydrolysable silanes containing a tertiary amine group and an ether or thioether linkage.

Abstract: The invention relates to a process for preparing urea-containing mercaptosilanes of the general formula I wherein a chlorosilane of the general formula II is reacted with NaSH in C2-C8 alcohol.

Abstract: The invention relates generally to transition metal salts, more specifically to iron, nickel, cobalt, manganese and ruthenium salts, activated with silylhydrides, and their use as efficient hydrosilylation catalysts.

Abstract: Metallocene compounds and pharmaceutical compositions containing these metallocene compounds are disclosed and described. Methods of treating cancer employing such metallocene compounds and pharmaceutical compositions also are provided.

Abstract: There is provided herein a method of making hydroxymethylphosphonate comprising reacting paraformaldehyde, at least one dialkyl phosphite and at least one trialkyl phosphite, in the presence of at least one amine catalyst.

Abstract: The thiol modified oligonucleotides have vast number of applications in the field of nucleic acid chemistry. The conjugates generated by mono thiol groups are unstable at higher temperature, in high salt concentration buffers and in presence other thiols. There is strong need to develop a novel thiol modifier probes that can generate multiple thiol groups. Described herein are efficient processes and compounds, dithiolane phosphoramidites derivative and dithiolane succinyl supports. The advantage of our cyclic disulfide thiol modifier is multifold a) each incorporation introduces two thiol groups; b) it can be introduced at any desired site of oligonucleotides; c) The symmetrical branching nature of the spacer in the linker arm of dithiolane allows for clean oligo synthesis, where cleavage of the linker arm and thereby of loss of oligo chain is prevented.

Abstract: The present invention is concerned with a staining dye for staining a biological cell, comprising dye molecules with a positively charged polar head group for attraction to cell membrane of the cell and for refraining the dye molecules from entering the cytoplasm, and one or more hydrophobic groups for interaction with phospholipids of the cell membrane. The dye molecules are phosphorescent transition metal polypyridine complexes having a metal center and ligands which are non-organic fluorophores.

Abstract: The invention provides a method for releasing capsular polysaccharide from S. aureus type 5 or type 8 cells, comprising the step of treating the cells with acid. The invention further provides a process for purifying capsular polysaccharide from S. aureus type 5 or type 8 cells comprising this method. Other processing steps may be included in the process, such as enzymatic treatment, e.g. to remove nucleic acid, protein and/or peptidoglycan contaminants; diafiltration, e.g. to remove low molecular weight contaminants; anion exchange chromatography, e.g. to remove residual protein; and concentration.

Abstract: The present disclosure provides novel imidazoquinoline derived compounds, derivatives thereof, analogues thereof, and pharmaceutically acceptable salts thereof, and methods of making and using such compounds. The present disclosure also provides TLR7 agonists and TLR7/TLR8 dual agonists, probes, tissue-specific molecules, adjuvants, immunogenic compositions, therapeutic compositions, and self-adjuvanting vaccines including the imidazoquinoline derived compounds, derivatives thereof, analogues thereof, and pharmaceutically acceptable salts thereof. Derivatives of the imidazoquinoline derived compounds also include dendrimers and dimers of the imidazoquinoline derived compounds, and methods of making and using the dendrimeic and dimeric imidazoquinoline derived compounds. The present disclosure also provides dual TLR2/TLR7 hybrid agonists that include imidazoquinoline derived compounds of the present disclosure.

Abstract: The invention relates to a compound which is, 2-[4-[(methylamino)carbonyl]-1H-pyrazol-1-yl]adenosine, which is a selective A2A adenosine receptor agonist in myocardial imaging. The new polymorph of 2-[4-[(methylamino)carbonyl]-1H-pyrazol-1-yl]adenosine (designated as polymorph E) is characterized by an X-ray diffraction pattern of X-RPD showing the following reflections at 2 Theta=5.8°, 12.3°, 15.9°, 17.3°, 20.5°, 22.6°, 23.6°, 27.7°, and 29.2°; and further characterized by a DSC scan showing marked endotherm in the range of 258 to 264° C.; and further characterized by a specific IR spectra.

Abstract: Disclosed herein are nucleosides, nucleotides and analogs thereof, pharmaceutical compositions that include one or more of nucleosides, nucleotides and analogs thereof, and methods of synthesizing the same. Also disclosed herein are methods of ameliorating and/or treating a disease and/or a condition, including an infection from a paramyxovirus and/or an orthomyxovirus, with a nucleoside, a nucleotide and an analog thereof.

Abstract: The present invention relates to compounds of formula (I), wherein R1, R2 and R3 are as described herein, and their prodrugs or pharmaceutically acceptable salt, enantiomer or diastereomer thereof, and compositions including the compounds and methods of using the compounds.

Abstract: A co-modified organopolysiloxane having a group having a siloxane dendron structure and a group containing a saccharide component (e.g. a sugar lactone amide alkyl group) is disclosed. The present invention also provides a method for producing the co-modified organopolysiloxane, as well as a surface treatment agent, a powder treatment agent, a powder composition, a powder-in-oil dispersion, a preparation for external use, and the like containing the co-modified organopolysiloxane.

Abstract: Methods and compositions for the selective derivatization of a oligohistidine-tagged recombinant protein. A modifying compound comprised of an imidazole reactive group, a linker, and a ligating group is contacted with the recombinant protein, and a cooperative bond forms between the ligating group and the oligohistidine tag in the presence of a metal cation, and a covalent bond forms between the imidazole reactive group and an imidazole ring of the oligohistidine tag followed by the concomitant separation of the imidazole reactive group from the linker. Addition of a metal chelator results in the dissociation of the ligating group and the oligohistidine tag.

Abstract: A method is disclosed for purifying an antibody monomer, comprising providing a porous membrane comprising a hydrophobic porous substrate, a hydrophilic molecular chain of a different material from that of the porous substrate, immobilized on the surface of pores of the porous substrate, and a side chain of the molecular chain, containing a nitrogen atom to which one to three alkyl groups each having two or three carbon atoms are bonded; passing an antibody solution containing antibody aggregates of dimers or higher-order multimers through the porous membrane to adsorb the antibody aggregates to the porous membrane; and recovering the purified antibody monomer in the passed solution.

Abstract: The present application relates to novel fluorinated epoxyketone-based compounds, compositions comprising these compounds and their use, in particular for the treatment of diseases, disorders or conditions mediated by proteasome inhibition, in particular, the present application includes compounds of Formula I, and compositions and uses thereof.

Abstract: The subject invention pertains to a modified MC1R peptide ligand comprising a peptide that is a melanocortin 1 receptor (MC1R) ligand and a functionality or linker, such as a click functionality, for conjugation to a surface or agent. The modified MC1R peptide ligand can be coupled, e.g., via a click reaction with a complementary click functionality attached, to a moiety to form an MC1R-targeted agent. Drugs, contrast agents, polymers, particles, micelles, surfaces of larger structures, or other moieties can be targeted to the MC1R. The subject invention also pertains to a MC1R peptide ligand-micelle complex comprising a peptide that is a melanocortin 1 receptor ligand connected via a click reaction product to a micelle. The micelle is stable in vivo and can target melanoma tumor cells by association of the peptide ligand with the MC1R or the tumor and selectively provide a detectable and/or therapeutic agent (such as an imageable contrast agent and/or anti-cancer agent) selectively to the tumor cell.

Abstract: The present disclosure provides peptides and peptide compositions, which facilitate the delivery of an active agent or an active agent carrier wherein the compositions are capable of penetrating the stratum corneum (SC) and/or the cellular membranes of viable cells.

Abstract: The present invention is directed to a recombinant fusion antigen gene, a recombinant fusion antigen protein and a subunit vaccine composition having the same against infection of porcine reproductive and respiratory syndrome virus (PRRSV). A recombinant fusion antigen gene, which encodes glycoprotein GP5 with truncated N?-terminal decoy epitope, a linker sequence and membrane protein M, followed by codon optimization, is expressed by a baculovirus expression system in vitro, thereby enhancing a yield of the recombinant fusion antigen protein. The recombinant fusion antigen protein can be applied in a subunit vaccine composition, for providing vaccinated animals with better protection ability without the risks of virulent spread and virulent recovery.

Abstract: The present invention includes the complete genome sequence for the methanogen, Methanobrevibacter ruminantium, including polynucleotides which encode M. ruminantium polypeptides or peptides, as well as polynucleotides from non-coding regions. Also included are the encoded M. ruminantium polypeptides and peptides, and antibodies directed to these peptides or polypeptides, in addition to expression vectors and host cells for producing these peptides, polypeptides, polynucleotides, and antibodies. The invention further includes methods and compositions for detecting, targeting, and inhibiting microbial cells, especially methanogen cells such as M. ruminantium cells, using one or more of the disclosed peptides, polypeptides, polynucleotides, antibodies, expression vectors, and host cells.

Abstract: The present invention relates to a soluble polypeptide comprised of repeat modules. More particularly, the present invention relates to a soluble fusion polypeptide of the N-terminal domain of internalin and LRR (Leucine rich repeat) family protein, a method for preparing the polypeptide, a vector comprising a nucleic acid sequence encoding the polypeptide, a host cell comprising the vector, a method for producing a solubility and folding-improved fusion polypeptide by expressing the vector in the host cell, and a method for improving the solubility and folding of the fusion polypeptide. Further, the present invention relates to a method for preparing the polypeptide bound with a specific target and analyzing the efficacy of the soluble polypeptide.

Abstract: The present invention relates to a novel gene derived from a tidal flat metagenome, and a novel protein obtained therefrom showing the coactivity of phospholipase and lipase. Specifically, the novel gene isolated from the metagenome library of tidal flat sediments and the protein having phospholipase and lipase activities encoded from the novel gene: are expressed in a water-soluble form to be mass-producible; enable ultra high-purity protein to be obtained through single step purification using an Ni-NTA column; show good activity in the pH range of 5˜10; maintain good low temperature activity and stability up to a temperature of 3° C. to 40° C.; and have high resistance against various organic solvents. Therefore, the novel gene and the protein can be usefully used for various industrial fields such as the purification and conversion of oil and fat, bio-medicine, and fine chemistry.

Abstract: Novel vaccines are provided that elicit broadly neutralizing anti-influenza antibodies. Some vaccines comprise nanoparticles that display hemagglutinin trimers from influenza virus on their surface. The nanoparticles comprise fusion proteins comprising a monomeric subunit of ferritin joined to at least a portion of an influenza hemagglutinin protein. Some portions comprise the ectodomain while some portions are limited to the stem region. The fusion proteins self-assemble to form the hemagglutinin-displaying nanoparticles. Some vaccines comprise only the stem region of an influenza hemagglutinin protein joined to a trimerization domain. Such vaccines can be used to vaccinate an individual against infection by heterologous influenza viruses and influenza virus that are antigenically divergent from the virus from which the nanoparticle hemagglutinin protein was obtained. Also provided are fusion proteins and nucleic acid molecules encoding such proteins.

Abstract: The disclosure generally relates to methods and materials for modulating cell productivity. In particular, the present disclosure provides polynucleotides and polypeptides that when overexpressed in microorganisms result in increased in productivity, such as increased biomass productivity. Also disclosed are methods of using the polynucleotides and polypeptides to modulate or increase productivity of host cells such as, for example, algal or heterokont cells. Genetically engineered host cells, such as algal and heterokont cells having increased biomass productivity and bioproducts derived from such host cells are also disclosed.

Abstract: The invention relates to a process for the preparation of hypoallergenic major birch pollen allergens by means of one or more chromatographic purification steps using essentially unbuffered aqueous bases as eluent and subsequent neutralization. The hypoallergenic major birch pollen allergens are distinguished by a lack of, but at least by reduced immunoglobulin E binding with simultaneous retention of therapeutically relevant T-cell stimulation. They can therefore be employed as low-side-effect therapeutic agents for specific immunotherapy.

Abstract: The present invention relates to the discovery of the Aegyptin gene and Aegyptin protein, a molecule that interacts with collagen and inhibits platelet adhesion, activation and aggregation. Novel biological tools, prophylactics, therapeutics, diagnostics, and methods of use of the foregoing are also disclosed.

Abstract: The present invention relates to novel analogs of PYY that have an improved therapeutic profile when compared to native human PYY. These novel PYY analogs are useful in the treatment of obesity, diabetes, and other disorders.

Abstract: [Problem] To provide a glycosylated polypeptide having affinity to somatostatin receptors and, compared to somatostatins, having improved in-blood stability. [Solution] The glycosylated polypeptide is characterized by at least two amino acids in a somatostatin or an analogue thereof being replaced by glycosylated amino acids.

Abstract: The invention relates to a peptide having a length of no more than 100 amino acids and comprising at least 19 contiguous amino acids from the amino acid sequence of the human PRAME protein, wherein the peptide comprises at least one HLA class II epitope and at least one HLA class I epitope from the amino acid sequence of the human PRAME protein and to its use as such or in a composition as a medicament for the treatment and/or prevention of cancer.