Abstract: The present invention relates to novel compounds that inhibit LRRK2 kinase activity, processes for their preparation, to compositions containing them and to their use in the treatment of or prevention of diseases characterized by LRRK2 kinase activity, for example Parkinson's disease, Alzheimer's disease and amyotrophic lateral sclerosis (ALS).

Abstract: The present invention provides compounds of formula 1: which are useful as inhibitors of TBK-1, pharmaceutical compositions thereof, methods for treatment of conditions associated with TBK1, processes for making the compounds and intermediates thereof.

Abstract: The present invention in one embodiment provides a compound of Formula I: or a pharmaceutically acceptable salt thereof, wherein the variables shown in Formula I are as defined in the specification.

Abstract: Disclosed herein are amido compounds that form covalent bonds with Bruton's tyrosine kinase (Btk). Also described are irreversible inhibitors of Btk. Also disclosed are pharmaceutical compositions that include the compounds. Methods of using the Btk inhibitors are disclosed, alone or in combination with other therapeutic agents, for the treatment of autoimmune diseases or conditions, heteroimmune diseases or conditions, cancer, including lymphoma, and inflammatory diseases or conditions.

Abstract: Pyrrolo[2,3-d]pyrimidine derivatives, and pharmaceutical acceptable salts thereof, useful in therapeutically treating patients with cancer are disclosed. These compounds selectively target folate receptors (FR) of cancerous tumor cells and inhibit purine synthesis and hence, DNA synthesis.

Abstract: The present invention provides for compounds of formula (I) wherein Rx, X, Y, Y1, L1, A1, A2, A3, A4, A5, A6, A7, and A8, have any of the values defined in the specification, and pharmaceutically acceptable salts thereof, that are useful as agents in the treatment of diseases and conditions, including inflammatory diseases, cancer, and AIDS. Also provided are pharmaceutical compositions comprised of one or more compounds of formula (I).

Abstract: This invention relates to processes and intermediates for making {1-{1-[3-fluoro-2-(trifluoromethyl)isonicotinoyl]piperidin-4-yl}-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile, useful in the treatment of diseases related to the activity of Janus kinases (JAK) including inflammatory disorders, autoimmune disorders, cancer, and other diseases.

Abstract: The present invention provides for compounds of formula (I) wherein X, Y, and R1 have any of the values defined in the specification, and pharmaceutically acceptable salts thereof, that are useful as agents in the treatment of diseases and conditions mediated and modulated by CFTR, including cystic fibrosis, Sjögren's syndrome, pancreatic insufficiency, chronic obstructive lung disease, and chronic obstructive airway disease. Also provided are pharmaceutical compositions comprised of one or more compounds of formula (I).

Abstract: A process for preparing materials derived from sugar alcohols such that the dehydration products exhibit better accountability and improved color to water-clear or near water-white appearance is described. In particular, the process involves employing a reducing Brønsted acid (e.g., phosphonic acid) for the catalysis of sugar alcohols to their corresponding dehydrated-cyclized products.

Abstract: This invention provides a compound represented by formula (1) or a pharmaceutically acceptable salt thereof. Specifically, the present invention provides a compound represented by formula (1) or a pharmaceutically acceptable salt thereof [Therein, A is O, S, or N—R6; ring G is a 5-membered or 6-membered aromatic ring, etc., including 1-3 heteroatoms selected from O, S and N as constituent atoms; R1 and R2 are each independently a hydrogen atom, a halogen atom, or an optionally-substituted C1-6 alkyl carbonyl group, etc.; R3, R4 and R5 are each independently a hydrogen atom, a halogen atom, or an optionally-substituted C1-6 alkyl carbonyl group, etc.; and R6 is a hydrogen atom or an optionally-substituted C1-6 alkyl group, etc.].

Abstract: Described herein are benzoxazepin oxazolidinone compounds with phosphoinositide-3 kinase (PI3K) modulation activity or function having the Formula I structure: or stereoisomers, tautomers, or pharmaceutically acceptable salts thereof, and with the substituents and structural features described herein. Also described are pharmaceutical compositions and medicaments that include the Formula I compounds, as well as methods of using such PI3K modulators, alone and in combination with other therapeutic agents, for treating diseases or conditions that are mediated or dependent upon PI3K dysregulation.

Abstract: The invention provides novel imidazol-piperidinyl derivatives of the formula (I) in which R1, R2, W, X1, X2, X3, X4 and n have the meanings indicated in formula I, and their manufacture and use for the treatment of hyperproliferative diseases, such as cancer.

Abstract: The present invention relates to compounds of formula I: in which p, q, Y1, Y2, R1, R2a, R2b, R3a, R3b, R4a, R4b, R5a, R5b, R7 and R8 are defined in the Summary of the Invention; capable of inhibiting the activity of SHP2. The invention further provides a process for the preparation of compounds of the invention, pharmaceutical preparations comprising such compounds and methods of using such compounds and compositions in the management of diseases or disorders associated with the aberrant activity of SHP2.

Abstract: The disclosure generally relates to compounds of formula I, including compositions and methods for treating human immunodeficiency virus (HIV) infection. The disclosure provides novel inhibitors of HIV, pharmaceutical compositions containing such compounds, and methods for using these compounds in the treatment of HIV infection.

Abstract: A Rifaximin polymorphic mixture of ?/? form in a relative ratio of 85/15±3 and a process for its preparation. The polymorphic mixture of Rifaximin is for use as a medicament, in particular in the treatment of traveler's diarrhea and hepatic encephalopathy. A pharmaceutical composition comprises the polymorphic mixture of Rifaximin as active ingredient, in particular, a solid formulation, more in particular, a film coated tablet. A polymorphic form of crude wet rifaximin and of purified wet rifaximin their use are used as intermediates in a process for the preparation of Rifaximin polymorphic mixture of ?/? form in a relative ratio of 85/15±3.

Abstract: The disclosure generally relates to compounds of formula I, including compositions and methods for treating human immunodeficiency virus (HIV) infection. The disclosure provides novel inhibitors of HIV, pharmaceutical compositions containing such compounds, and methods for using these compounds in the treatment of HIV infection.

Abstract: 18F-labeled 4-boronophenylalanine (BPA) can be produced by preparing and further processing a precursor of 18F-labeled BPA represented by the following formula: in which R1 represents a bromo group, an iodo group, a fluoro group, a diazaborinane derivative, BX3? or BX3?M+ (wherein X represents a halogen atom; and M+ represents a monovalent monoatomic cation, a polyatomic cation or a complex cation).

Abstract: The invention provides a method of preparing a 89Zr-oxine complex of the formula. The invention also provides a method of labeling a cell with the 89Zr-oxine complex and a method for detecting a biological cell in a subject comprising administering the 89Zr-oxine complex to the subject.

Abstract: This invention relates to novel bridged bis indenyl metallocene catalyst compounds where the bridge is —((R15*)2Si—Si(R15)2)— wherein, each R15 and R15* is identical or different and is a substituted or unsubstituted, branched or unbranched C1-C20 alkyl group, preferably each R15 together do not form a ring, and/or each R15* together do not form a ring, and/or R15 and R15* together do not form a ring. This invention also relates to polymerization processes to produce polymer and to polymer compositions produced by the methods described.

Abstract: Described is a production process for the preparation of an organic titanium derivative useful for the preparation of yellow inks for digital printing on ceramics, comprising the following steps: (i) mixing an organic and/or inorganic compound of titanium (IV) and a 1,3-diol of formula: wherein R1, R2, R3 and R4 are independently selected from H and a linear or branched C1-C6 alkyl radical, in the presence of at least an organic solvent immiscible with water and subsequent removal of reaction by-products; (ii) adding water to the reaction mixture in a H2O:Ti?2 molar ratio and subsequent removal of unreacted water and reaction by-products; (iii) maturing the reaction mixture at a temperature of 180-200° C. for 16-50 hours. Also described are the titanium derivative obtainable by means of the above-reported process, an ink that contains the derivative and a method of digital printing on ceramics that uses said ink.

Abstract: The present invention provides a compound of formula I; or a pharmaceutically acceptable salt thereof, wherein R1, R2 and R3 are defined herein. The invention also relates to a method for manufacturing the compounds of the invention, and its therapeutic uses. The present invention further provides pharmaceutical composition of the compounds of the invention and a combination of pharmacologically active agents and a compound of the invention.

Abstract: The present invention relates to compounds of formula (I) or pharmaceutically acceptable salts thereof, wherein X, Y, Z, R1-R11, m, n, and p are defined herein. The novel pyrimidine derivatives are useful in the treatment of abnormal cell growth, such as cancer, in mammals. Additional embodiments relate to pharmaceutical compositions containing the compounds and to methods of using the compounds and compositions in the treatment of abnormal cell growth in mammals.

Abstract: The invention encompasses the novel class of compounds represented by the Formula (I) below, which are inhibitors of the TC-PTP enzyme. The invention also encompasses pharmaceutical compositions which include the compounds shown above and methods of treating or preventing TC-PTP mediated diseases, including cancer, via their use in the activation of antigen-presenting cells, like dendritic cells, for applications in the immunotherapeutic treatment of diseases.

Abstract: The present inventors prepared novel benzoxaphosphole compounds and shown a process for the synthesizing these novel compounds. The process of preparing the compounds is simple, transition metal free and gives product with high yield. The synthesized benzoxaphosphole compounds are expected to show potential biological.

Abstract: The present invention relates to a method of membrane-filtrating a lignin containing composition in order to obtain a lignin fraction more suitable for further treatments. In particular it relates to treating a liquid lignin composition to obtain a lignin fraction having a desired molecular weight distribution by a membrane filtration. It comprises subjecting the liquid lignin composition to a first membrane filtration with a first filter cut-off adapted to remove species having a first molecular weight thereby providing a permeate with a molecular weight distribution defined by said cut-off. Then, the permeate from the first membrane filtration is; subjected to at least one further filtration step with a second filter cut-off, different from said first filter cut-off to provide a retentate (concentrate) with a molecular weight distribution defined by both the cut-off in the first filter the cut-off in said second filter.

Abstract: Acrylamide-based conductive compounds, and methods of making and using the acrylamide-based conductive compounds are disclosed. The acrylamide-based conductive compounds may include monomers or may be formed into polymers and acrylamide-based conductive materials, such as gels. The acrylamide-based conductive materials may be formed using inflammable or high boiling point fluids. The acrylamide-based conductive compounds described herein may conduct, coordinate, or otherwise be associated with various ions, including, without limitation, lithium ions, sodium ions and potassium ions. As such, acrylamide-based conductive compound may be used to support ion movement within electrical components and/or power devices such as batteries and capacitors.

Abstract: A binder comprising a polymeric binder comprising the products of a carbohydrate reactant and nucleophile is disclosed. The binder is useful for consolidating loosely assembled matter, such as fibers. Fibrous products comprising fibers in contact with a carbohydrate reactant and a nucleophile are also disclosed. The binder composition may be cured to yield a fibrous product comprising fibers bound by a cross-linked polymer. Further disclosed are methods for binding fibers with the carbohydrate reactant and polyamine based binder.

Abstract: The present invention provides preparations of monosaccharides, disaccharides, trisaccharides, and pentasaccharides of heparinoids. The present invention also provides novel monosaccharides, disaccharides, trisaccharides and pentasaccharides for use in the preparation of heparinoids.

Abstract: The present disclosure encompasses solid state forms of Sofosbuvir and pharmaceutical compositions thereof.

Abstract: The present invention relates to compositions and methods for preparing splice variants of TNFalpha receptor (TNFR) in vivo or in vitro, and the resulting TNFR protein variants. Such variants may be prepared by controlling the splicing of pre-mRNA molecules and regulating protein expression with splice switching oligonucleotides or splice switching oligomers (SSOs). The preferred SSOs according to the invention target exon 7 or 8 of TNFR1 (TNFRSF1A) or TNFR2 (TNFRSF1A) pre-mRNA, typically resulting in the production of TNFR variants which comprise a deletion in part or the entire exon 7 or 8 respectfully. SSOs targeting exon 7 are found to result in a soluble form of the TNFR, which has therapeutic benefit for treatment of inflammatory diseases. The SSO's are characterized in that they are substantially incapable or incapable of recruiting RNaseH.

Abstract: Provided herein are compositions comprising nucleic acid structures comprising three or more arms arranged at fixed angles from each other, composites thereof such as DNA cages, and methods for their synthesis and use.

Abstract: The present invention relates to a detection unit comprising a solid surface and a partially neutral single-stranded oligonucleotide comprising a first portion. The first portion is attached to the solid surface; the length of the first portion is about 50% of the total length of the partially neutral single-stranded oligonucleotide; and the first portion comprises at least one neutral nucleotide and at least one unmodified nucleotide. The invention improves the detection sensitivity and accuracy of the detection of biomolecules.

Abstract: The invention relates to 2,4,6-octatrienoic acid derivative compounds having general formula (I) (CH3—CH?CH—CH?CH—CH?CH—CO—O—)n—R (I) consisting of esters wherein n=1, 2, 3 and wherein R is selected from alkyl, aryl or cycloalkyl of a polyol, phenol or phenolic acid; or consisting of a salt wherein n=1 and R=arginine, as active ingredients in a pharmaceutical or cosmetic composition having a combined antioxidant activity against free radicals together with an anti-inflammatory action.

Abstract: Disclosed is a method for refolding a protein or peptide that does not contain essential disulfides and that contains at least one free cysteine residue. Also disclosed are polymer IFN-? conjugates that have been created by the chemical coupling of polymers such as polyethylene glycol moieties to IFN-?, particularly via a free cysteine in the protein. Also disclosed are analogs of bioactive peptides that may be used to create longer acting versions of the peptides, including analogs of glucagon, glucagon-like peptide-1 (GLP-1), GLP-2, Gastric inhibitory peptide (GIP), PYY, exendin, ghrelin, gastrin, amylin, and oxyntomodulin.

Abstract: Herein is reported a method for the purification of an antibody directly captured from clarified cell culture supernatants using Streamline CST and/or Capto MMC, wherein especially product related (aggregates and fragments) and process related impurities (host cell protein, media components) could efficiently be removed, resulting in a preparation with a purity comparable to classical protein A affinity chromatography.

Abstract: Provided are methods of treating a cancer characterized by the presence of a mutant allele of IDH1/2 comprising administering to a subject in need thereof a compound described here.

Abstract: The present application describes organic compounds of Formula (I) and pharmaceutical compositions thereof, and their use for the treatment, prevention and/or amelioration of diseases, particularly bacterial infections.

Abstract: Pyrrole compounds as Granzyme B inhibitors, compositions that include the compounds, and methods for using the compounds. Method for treating cutaneous scleroderma, epidermolysis bullosa, radiation dermatitis, alopecia areata, and discoid lupus erythematosus are provided.

Abstract: Proline compounds as Granzyme B inhibitors, compositions that include the compounds, and methods for using the compounds. Methods for treating cutaneous scleroderma, epidermolysis bullosa, radiation dermatitis, alopecia areata, and discoid lupus erythematosus are provided.

Abstract: Covalent Granzyme B inhibitors, compositions that include the compounds, and methods for using the compounds. A method for treating cutaneous scleroderma, epidermolysis bullosa, radiation dermatitis, alopecia areata, and discoid lupus erythematosus are provided.

Abstract: Novel polypeptides comprising a chemokine-binding peptide and an Fc fragment are disclosed. The polypeptides are capable of binding to certain chemokines so as to modulate their activity. These polypeptides can be used to modulate in vivo chemokine-dependent processes such as inflammation and autoimmunity, and to treat associated conditions.

Abstract: The present invention relates to a compound of the following formula (I): in which at least one and only one group chosen among R5, R6 and R7 is a group of the following formula: The present invention relates also to uses thereof for preservation and/or protection and/or regeneration of biological materials and or microorganisms and for cosmetic or dermato logical applications such as anti-aging, skin protection and skin regeneration; to culture, storage and/or preservation media comprising such a compound; to cosmetic or dermato logical compositions comprising such a compound; to processes for preparing such a compound; and to synthesis intermediates.

Abstract: Provided are cyclic peptide analogs, conjugates comprising such compounds, and pharmaceutical compositions comprising such compounds and conjugates, and methods of treating cancer with such compounds and conjugates.

Abstract: Expression vectors and mammalian cell lines containing them are described that enable the recombinant production of HIV-1 envelope proteins, including SOSIP modified gp140 trimers capable of inducing broadly neutralizing antibodies.

Abstract: Some embodiments of the invention include inventive polypeptides (e.g., mutant VP2 proteins) and virus-like particles made from the inventive polypeptides. Other embodiments of the invention include compositions for treating (e.g., preventing) parvovirus (e.g., erythrovirus or parvovirus B19) infection and other diseases. Further embodiments include methods for administering compositions to an animal. Other embodiments include treating (e.g., preventing) par vovirus (e.g., erythrovirus or parvovirus B19) infection and other diseases. Still other embodiments include nucleic acid sequences that encode the inventive polypeptides. Additional embodiments of the invention are also discussed.

Abstract: Provided in the present invention are a diphtheria toxin non-toxic mutant CRM197 or a fragment thereof as an adjuvant in a fusion protein and the use thereof to enhance the immunogenicity of a target protein fused therewith, for example, an HEV capsid protein, or an influenza virus M2 protein or an immunogenic fragment thereof. Also provided is a method for enhancing the immunogenicity of a target protein, comprising the fusion expression of the CRM197 or the fragment thereof with the target protein to form a fusion protein. Further provided is a fusion protein comprising the CRM197 or the fragment thereof and a target protein, the CRM197 or the fragment thereof enhancing the immunogenicity of the target protein. The present invention also provides an isolated nucleic acid encoding the fusion protein, a construct and a vector comprising said nucleic acid, and a host cell comprising the nucleic acid.

Abstract: This disclosure provides methods and compositions related to microbial gene expression. In one aspect, a synthetic polypeptide having a xylose import activity.

Abstract: The present invention relates to a cobalamin acquisition protein, compositions containing the cobalamin acquisition protein, and the use of such compositions.

Abstract: The present invention provides methods of designing and making structurally stabilized anti-microbial peptides for the prophylaxis and treatment of infection. Methods are also disclosed for designing stabilized anti-microbial peptides that are selectively lytic/cytotoxic to bacteria, allowing for internal use of anti-microbial peptides without mammalian membrane disruption and cytotoxicity.

Abstract: Tau protein has a causative role in Alzheimer's disease and multiple other neurodegenerative disorders exhibiting tau histopathology collectively termed tauopathies. The primary function of tau protein is to facilitate assembly and maintenance of microtubules in neuronal axons. In the disease process tau protein becomes modified, loses its affinity to microtubules and accumulates in the cell body where it forms aggregates. The large neurofibrillary tangles formed from tau protein assembled into filaments were thought to be the pathological structure of tau. However, more recent work indicates that smaller, soluble oligomeric forms of tau are best associated with neuron loss and memory impairment. Here, novel compositions of tau oligomers and novel mechanisms for tau oligomer nucleation, extension and termination are taught.