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.

Abstract: The present invention provides compounds of Formula (I) or stereoisomers, tautomers, or pharmaceutically acceptable salts thereof, wherein all the variables are as defined herein. These compounds are selective Factor XIa inhibitors or dual inhibitors of FXIa and plasma kallikrein. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating thromboembolic and/or inflammatory disorders using the same.

Abstract: The present invention provides a heterocyclic compound having a HDAC inhibitory action, and useful for the treatment of autoimmune diseases and/or inflammatory diseases, graft versus host disease, cancers, central nervous diseases including neurodegenerative diseases and the like, and a medicament comprising the compound. 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 invention provides a compound of Formula I: or a pharmaceutically acceptable salt thereof, and the use of compounds of Formula I for treatment of neurodegenerative diseases and disorders, such as Alzheimer's disease.

Abstract: The invention provides novel 8-azabicyclo[3.2.1]octane compounds of formula (I): wherein R1, R2, R3, A, and G are defined in the specification, or a pharmaceutically-acceptable salt or solvate thereof, that are antagonists at the mu opioid receptor. The invention also provides pharmaceutical compositions comprising such compounds, methods of using such compounds to treat conditions associated with mu opioid receptor activity, and processes and intermediates useful for preparing such compounds.

Abstract: The invention provides novel compounds having the general formula: wherein R1, R2, R3, R4, R5, R6, X, Y, W and n are as described herein, compositions including the compounds and methods of using the compounds.

Abstract: Disclosed herein are compounds that inhibit the activity of anti-apoptotic Bcl-2 proteins, compositions containing the compounds and methods of treating diseases using the compounds. One embodiment of such compounds is 4-(4-{[2-(4-chloro-2-fluorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl)amino]phenyl}sulfonyl)-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide.

Abstract: Amide derivatives and pharmaceutically acceptable salts thereof, preparation method thereof and medicinal application thereof are provided. Specifically, amide derivatives represented by general formula (I) are provided. The amide derivatives represented by general formula (I) can be used as a therapeutic agent, particularly as an inhibitor for microsomal prostaglandin E synthase-1 (mPGES-1), and also to treat and/or prevent diseases or illnesses such as inflammation and/or pain etc. The definition of each substituent group in general formula (I) is the same as the definition in the description.

Abstract: The present invention relates to a radioactive halogen-labeled pyrido[1,2-a]benzimidazole derivative compound represented by a specific general formula or a salt thereof, or a radiopharmaceutical comprising the same.

Abstract: Indazole compounds for treating various diseases and pathologies are disclosed. More particularly, the present invention concerns the use of an indazole 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: Described herein are carboxamide derivatives of Formula (II) that are useful as inhibitors of p90 ribosomal S6 kinase (RSK), pharmaceutical compositions comprising the derivatives, and methods of using the derivatives in treating diseases or conditions associated with RSK activity: wherein R2, R4a, R4b, R11, R12, and n are defined in the specification.

Abstract: The present invention relates to novel adenine based inhibitors of adenylyl cyclase of the formula: wherein X, L, R1, R2, R5 are those defined herein. Compounds of the present invention are useful to treat cardiovascular diseases. The present invention also relates to a method of preventing heart failure by administering an effective amount of compound according to the invention following vascular injury and reperfusion therapy.

Abstract: The present invention relates to a compound represented by chemical formula 1, which can be used for the prevention and treatment of diseases caused by abnormality in a prolyl-tRNA synthetase (PRS) activity, or a pharmaceutically acceptable salt thereof, a method for preparing the same, and a pharmaceutical composition comprising the same.

Abstract: A novel substituted N-(pyrrolidin-3-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine and a use thereof as a Janus kinase (JAK) inhibitor are provided.

Abstract: Methods are provided for efficient preparation of hydromorphone or hydrocodone by redox isomerization of morphine or codeine allylic alcohols, respectively, using transition metal aminophosphine catalysts formed in situ.

Abstract: The present invention relates to pyrazole compounds, and pharmaceutically acceptable compositions thereof, useful as positive allosteric modulators of follicle stimulating hormone receptor (FSHR).

Abstract: The present invention is directed to polyisocyanates and polyurethanes derived therefrom. In various embodiments, the present invention provides polyisocyanates, methods of making the polyisocyanates from fused bicyclic alcohols, polyurethanes, and methods of making the polyurethanes from the polyisocyanates.

Abstract: The present invention relates to novel pyrimido-diazepinone compounds, methods of modulating protein kinases, including MPS1 (TTK), ERK5 (BMK1, MAPK7), polo kinase 1, 2, 3, or 4, Ack1, Ack2, Abl, DCAMKL1, ABL1, Abl mutants, DCAMKL2, ARK5, BRK, MKNK2, FGFR4, TNK1, PLK1, ULK2, PLK4, PRKD1, PRKD2, PRKD3, ROS1, RPS6KA6, TAOK1, TAOK3, TNK2, Bcr-Abl, GAK, cSrc, TPR-Met, Tie2, MET, FGFR3, Aurora, Axl, Bmx, BTK, c-kit, CHK2, Flt3, MST2, p70S6K, PDGFR, PKB, PKC, Raf, ROCK-H, Rsk1, SGK, TrkA, TrkB and TrkC, and the use of such compounds in the treatment of various diseases, disorders or conditions.

Abstract: The invention relates to novel methods for preparing indolinobenzodiazepine dimer compounds and their synthetic precursors.

Abstract: Compounds of formula (I), wherein the substituents are as defined in claim 1, and the agrochemically acceptable salts salts, stereoisomers, enantiomers, tautomers and N-oxides of those compounds, can be used as insecticides and can be prepared in a manner known per se.

Abstract: Hydridosilapyrroles and hydridosilaazapyrrole are a new class of heterocyclic compounds having a silicon bound to carbon and nitrogen atoms within the ring system and one or two hydrogen atoms on the silicon atom. The compounds have formula (I): in which R is a substituted or unsubstituted organic group and R? is an alkyl group. These compounds react with a variety of organic and inorganic hydroxyl groups by a ring-opening reaction and may be used to produce silicon nitride or silicon carbonitride films.

Abstract: A method for preparing a reaction product including an aryl-functional silane includes sequential steps (1) and (2). Step (1) is contacting, under silicon deposition conditions, (A) an ingredient including (I) a halosilane such as silicon tetrahalide and optionally (II) hydrogen (H2); and (B) a metal combination comprising copper (Cu) and at least one other metal, where the at least one other metal is selected from the group consisting of gold (Au), cobalt (Co), chromium (Cr), iron (Fe), magnesium (Mg), manganese (Mn), nickel (Ni), palladium (Pd), and silver (Ag); thereby forming a silicon alloy catalyst comprising Si, Cu and the at least one other metal. Step (2) is contacting the silicon alloy catalyst and (C) a reactant including an aryl halide under silicon etching conditions.

Abstract: The invention relates to a method of preparing monocyclic aromatic compounds from lignin and to the use of the method and/or the aromatic compounds obtained by the method according to the invention in the production of fuels, electronic components, plastic polymers, rubber, medicines, vitamins, cosmetic products, perfumes, foodstuffs, synthetic threads and fibers, synthetic leathers, adhesives, pesticides and fertilizers. The invention also relates to a method of producing fuels, electronic components, plastic polymers, rubber, medicines, vitamins, cosmetic products, perfumes, foodstuffs, synthetic threads and fibers, synthetic leathers, adhesives, pesticides and fertilizers, including a step of preparing aromatic compounds from lignin using the method according to the invention.

Abstract: Compounds, methods of use, and processes for making inhibitors of complement factor D comprising formula I, or a pharmaceutically acceptable salt or composition thereof wherein R12 or R13 on the A group is an aryl, heteroaryl or heterocycle (R32) are provided. The inhibitors described herein target factor D and inhibit or regulate the complement cascade at an early and essential point in the alternative complement pathway, and reduce factor D's ability to modulate the classical and lectin complement pathways. The inhibitors of factor D described herein are capable of reducing the excessive activation of complement, which has been linked to certain autoimmune, inflammatory, and neurodegenerative diseases, as well as ischemia-reperfusion injury and cancer.

Abstract: Compounds that have agonist activity at one or more of the S1P receptors are provided. The compounds are sphingosine analogs that, after phosphorylation, can behave as agonists at S1P receptors.

Abstract: The present invention relates to Phosphate Substituted Quinolizine Derivatives of Formula (I): and pharmaceutically acceptable salts or prodrug thereof, wherein X, Y, R1, R2, R3, R4, R5, R9 and R10 are as defined herein. The present invention also relates to compositions comprising at least one Phosphate Substituted Quinolizine Derivative, and methods of using the Phosphate Substituted Quinolizine Derivatives for treating or preventing HIV infection in a subject.

Abstract: The present disclosure is in relation to the field of nanotechnology and cancer therapeutics. In particular, the present disclosure relates to platinum based compounds comprising platinum moiety, linker moiety and lipid moiety and corresponding nanoparticles thereof. The disclosure further relates to synthesis of said platinum based compounds, nanoparticles and compositions comprising said platinum based compounds/nanoparticles. The disclosure also relates to methods of managing cancer by employing aforesaid carbene compounds, platinum based compounds, nanoparticles and compositions thereof.

Abstract: A transition metal amino borohydride material includes a first row transition metal in conjunction with an amine ligand and borohydride, in a condition of having been thermally treated to a temperature of at least 70° C. and up to but not including 800° C. An exemplary such material, Fe(DETA)(BH4)2 having been heat treated at 300° C., had good hydrogen storage characteristics.

Abstract: Catalysts prepared from abundant, cost effective metals, such as cobalt, nickel, chromium, manganese, iron, and copper, and containing one or more neutrally charged ligands (e.g., monodentate, bidentate, and/or polydentate ligands) and methods of making and using thereof are described herein. Exemplary ligands include, but are not limited to, phosphine ligands, nitrogen-based ligands, sulfur-based ligands, and/or arsenic-based ligands. In some embodiments, the catalyst is a cobalt-based catalyst or a nickel-based catalyst. The catalysts described herein are stable and active at neutral pH and in a wide range of buffers that are both weak and strong proton acceptors. While its activity is slightly lower than state of the art cobalt-based water oxidation catalysts under some conditions, it is capable of sustaining electrolysis at high applied potentials without a significant degradation in catalytic current. This enhanced robustness gives it an advantage in industrial and large-scale water electrolysis schemes.

Abstract: There is provided a method for the chlorination of a sucrose-6-acylate to produce a 4,1?,6?-trichloro-4,1?,6?-trideoxy-galactosucrose-6-acylate, wherein said method comprises the following steps (i) to (v): (i) providing a first component comprising sucrose-6-acylate; (ii) providing a second component comprising a chlorinating agent; (iii) combining said first component and said second component to afford a mixture; (iv) heating said mixture for a heating period in order to provide chlorination of sucrose-6-acylate at the 4, 1? and 6? positions thereof; (v) quenching said mixture to produce a 4,1?,6?-trichloro-4,1?,6?-trideoxy-galactosucrose-6-acylate; wherein at least one of said first component and said second component comprises a reaction vehicle, and said reaction vehicle comprises a tertiary amide; and wherein said mixture comprises a cosolvent during a least a portion of the heating period of step (iv), wherein said cosolvent comprises dimethylacetamide (DMAc).

Abstract: A method for purifying epidaunorubicin is provided. The purification method involves the removal of the impurity epi-feudomycin, which is formed as a by-product in the biotechnological production of epidaunorubicin.

Abstract: The present invention provides a method for preparing a 6-aminohexyl lactoside-NOTA conjugate. The preparation method comprises brominating perbenzoylated lactose with hydrobromic acid; glycosylating 6-azidohexanol to obtain 6-azidohexyl perbenzoyl lactoside; and deprotecting this precursor in two steps to obtain 6-aminohexyl lactoside and conjugating 6-aminohexyl lactoside to NCS-benzyl-NODA GA (i.e. 2,2?-(7-(1-carboxy-4-((4-isothiocyanate benzyl) amino)-4-oxobutyl)-1,4,7-triazonane-1,4-diyl) diacetic acid) in triethyl amine as an alkaline solvent, to obtain a 6-aminohexyl lactoside-NCS-benzyl-NODA GA conjugate. In this novel preparation method, no deglycosylated side product is produced, such that the yield is considerably increased to 46%. Therefore, the method is suitable for future massive production since the requirement for repeated preparations for massive production is reduced, and the impurities produced in the previously scaled-up preparation process are not present.

Abstract: The present invention provides stapled polypeptides of the Formulae (I) and (VI): (I) (VI) and salts thereof; wherein the groups ; R1a, R1b, R1c, R2a, R3a, R2b, R3b, R4a, R4b, RA, RZ, L1a, L1b, L2, L3, XAA, v, w, p, m, s, n, t, and q are as defined herein. The present invention further provides methods of preparing the inventive stapled polypeptides from unstapled polypeptide precursors. The present invention further provides pharmaceutical compositions comprising a stapled polypeptide of Formula (I) or (VI), and methods of using the stapled peptides. The present invention also provides modifications of the staples post ring closing metathesis.

Abstract: The present invention relates to compounds that are cationic vancomycin analogs and their compositions. Method of making the compounds and their use as medicament for the treatment of bacterial infection are also disclosed.

Abstract: The present invention provides cyclic depsipeptide compounds of formula (I) and compositions comprising the compounds that are effective against parasites that harm animals. The compounds and compositions may be used for combating parasites in or on mammals and birds. The invention also provides for an improved method for eradicating, controlling and preventing parasite infestation in birds and mammals.

Abstract: The present invention relates to a biosynthetic random coil polypeptide or a biosynthetic random coil polypeptide segment or biosynthetic conjugate, in which the biosynthetic random coil polypeptide, the biosynthetic random coil polypeptide segment, or the biosynthetic conjugate comprises an amino acid sequence consisting solely of proline and alanine amino acid residues, wherein the amino acid sequence consists of at least about 50 proline (Pro) and alanine (Ala) amino acid residues. The at least about 50 proline (Pro) and alanine (Ala) amino acid residues may be (a) constituent(s) of a heterologous polypeptide or an heterologous polypeptide construct. Also uses and methods of use of these biosynthetic random coil polypeptides or polypeptide segments or conjugates are described.

Abstract: The instant application provides methods and related compositions pertaining to novel HIV envelope proteins. In some embodiments, the invention relates to methods and compositions for the preparation, production, and administration of isolated novel HIV envelope nucleic acid and protein sequences suitable, for example, as vaccines against HIV.

Abstract: A modified adeno-associated virus (AAV) capsid protein comprising at least one non-native amino acid that confers to the modified AAV particles new properties, such as increased transduction efficiency and reduced immunogenicity. These modified AAV proteins and particles are particularly useful for gene therapy and the treatment of various diseases and conditions.

Abstract: This invention refers to polynucleotides and non-hemorrhagic and non-immunogenic polypeptides of selective immunosuppressive activity on production of antibodies to antigens of different natures. The polypeptides described herein are useful for preparing pharmaceutical compositions for prevention or treatment of conditions that require immunosuppression, preferably, inflammatory, autoimmune, allergic and infectious diseases and rejection to transplanted organs.

Abstract: Disclosed herein are methods and compositions for insertion of transgene sequences encoding proteins that is aberrantly expressed in disease or disorder such as a lysosomal storage disease.

Abstract: Provided herein are biologically active single chain relaxin peptides. In particular the present invention relates to single chain relaxin peptides comprising a B chain derived from relaxin-2, the peptide being truncated by one or more amino acid residues at the N-terminus with respect to the sequence of the B chain of native relaxin-2. Typically the single chain relaxin peptides selectively bind to the RXFP1 receptor.

Abstract: The present invention relates to methods and systems for increasing the affinity of a T cell receptor (TCR) to its ligand by subjecting the TCR gene to somatic hypermutation. The present invention further relates to use of affinity maturated TCRs to create T cells reactive against a selected antigen.

Abstract: The present invention relates to peptides, proteins, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer. The present invention furthermore relates to tumor-associated T-cell peptide epitopes, alone or in combination with other tumor-associated peptides that can for example serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses, or to stimulate T cells ex vivo and transfer into patients. Peptides bound to molecules of the major histocompatibility complex (MHC), or peptides as such, can also be targets of antibodies, soluble T-cell receptors, and other binding molecules.

Abstract: The present invention relates to peptides, proteins, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer. The present invention furthermore relates to tumor-associated T-cell peptide epitopes, alone or in combination with other tumor-associated peptides that can for example serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses, or to stimulate T cells ex vivo and transfer into patients. Peptides bound to molecules of the major histocompatibility complex (MHC), or peptides as such, can also be targets of antibodies, soluble T-cell receptors, and other binding molecules.

Abstract: A recombinant or isolated integrin heterodimer comprising a novel subunit ?10 in association with a subunit ? is described. The ?10 integrin may be purified from bovine chondrocytes on a collagen-type-II affinity column. The integrin or the subunit of ?10 can be used as a marker or target of all types of cells, e.g. of chondrocytes, osteoblasts, and fibroblasts. The integrin or the subunit ?10 thereof can be used as a marker or target in different physiological or therapeutic methods. They can also be used as active ingredients in pharmaceutical compositions and vaccines.

Abstract: A composition including an elastin-like polypeptide (ELP) coupled to a therapeutic agent is provided. The ELP comprises at least about 5 repeats of the amino acid sequence VPGXG. Further provided is a method of using the composition for therapeutic agent delivery during pregnancy to reduce the amount of the therapeutic agent crossing a placenta in a pregnant subject. The method includes administering to the pregnant subject an effective amount of the composition comprising the ELP coupled to the therapeutic agent.

Abstract: Disclosed are modified pigment epithelium-derived factor (PEDF) peptides, particulate carrier prodrugs thereof, and pharmaceutical compositions comprising the peptides or particulate carrier prodrugs. The peptides, particulate carrier prodrugs, and pharmaceutical compositions may be used to treat diseases and disorders that are amenable to treatment with anti-angiogenic agents, anti-tumorigenic agents, anti-fibrotic agents, chemotherapy-protecting agents, and immune stimulating agents.

Abstract: The present invention addresses a need for improved treatments for Filovirus infections.

Abstract: The present invention provides monoclonal antibodies, or antigen-binding fragments thereof, that bind to Ebola virus glycoproteins, pharmaceutical compositions comprising the antibodies and methods of use. The antibodies of the invention are useful for inhibiting or neutralizing Ebola virus activity, thus providing a means of treating or preventing Ebola virus infection in humans. In some embodiments, the invention provides for use of one or more antibodies that bind to the Ebola virus for preventing viral attachment and/or entry into host cells. The antibodies of the invention may be used prophylactically or therapeutically and may be used alone or in combination with one or more other anti-viral agents or vaccines.

Abstract: This invention is directed to an antibody construct or fragment thereof derived from an RSV-infected human, such that the antibody construct binds with specificity to RSV fusion protein antigenic region II/A with an affinity of greater than 1×10?9M. Preferably, the antibody construct is capable of neutralizing RSV strains, including at least one RSV strain that is resistant to palivizumab. The invention further relates to nucleic acids encoding the antibody construct or portions thereof, and cell lines expressing the antibody. This invention further relates to methods for producing said antibody construct, and to the use of said antibody construct for treating or preventing infection of a patient by RSV having a normal or mutated version of F protein.