Abstract: Provided herein are solid state forms of Vemurafenib hydrochloride, processes for preparing the solid state forms, as well as pharmaceutical compositions and formulations comprising said solid state forms.

Abstract: The present invention relates to naphthyridine and isoquinoline compounds, and pharmaceutically acceptable compositions thereof, useful as inhibitors of CDK8/19, and for the treatment of CDK8/19-related disorders.

Abstract: The present application provides novel substituted quinazoline and pyrido-pyrimidine compounds and pharmaceutically acceptable salts, prodrugs, and solvates thereof. Also provided are methods for preparing these compounds. These compounds are useful in co-regulating PI3K and/or mTOR activity by administering a therapeutically effective amount of one or more of the compounds to a patient. By doing so, these compounds are effective in treating conditions associated with the dysregulation of the PI3K/AKT/mTOR pathway. Advantageously, these compounds perform as dual PI3K/mTOR inhibitors. A variety of conditions can be treated using these compounds and include diseases which are characterized by inflammation or abnormal cellular proliferation. In one embodiment, the disease is cancer.

Abstract: Compounds of formula (I) described herein are p38 MAPK inhibitors and are useful as anti-inflammatory agents in the treatment of, inter alia, diseases of the respiratory tract

Abstract: The present invention relates to tricyclic quinoline and quinoxaline derivatives, to a pharmaceutical composition containing such compounds, to their use as modulators, especially agonists or partial agonists, of the 5-HT2C receptor, their use for preparing a medicament for the prevention or treatment of conditions and disorders which respond to the modulation of 5-HT2C receptor, and to a method for preventing or treating conditions and disorders which respond to the modulation of 5-HT2C receptor.

Abstract: A process for preparation of a sodium salt of (2S, 5R)-2-carboxamido-7-oxo-6-sulfooxy-1,6-diaza-bicyclo[3.2.1]octane is disclosed which is comprising the amidation of a compound of Formula (II) to obtain a compound of Formula (III).

Abstract: The present invention relates to a compound represented by the following formula (1): wherein W, X, Y, R1, R2, R33, R34, m and n are as defined in the claims, or a pharmacologically acceptable salt thereof.

Abstract: Chemical compounds that modulate kinase activity, including PI3 kinase activity, and chemical compounds, pharmaceutical compositions, and methods of treatment of diseases and conditions associated with kinase activity, including P13 kinase activity, are described herein.

Abstract: Flumazenil (FMZ) is labeled with fluorine(F)-18 to obtain F-18-flumazenil. F-18-flumazenil can be strongly combined with type-A acceptor of gamma-aminobutyric acid (GABAA) in brain for tracing. The time and temperature for labeling is saved and lowered. The toxic chemical, acetonitrile, used in separation and purification can be prevented. The present invention has a simplified procedure for evaluating mental disease medicines in a short time. Moreover, time for developing medicines for treating related diseases of the central nervous system can be reduced.

Abstract: The present invention relates to substituted imidazopyridazine compounds, to methods of preparing said compounds, to pharmaceutical compositions and combinations comprising said compounds and to the use of said compounds for manufacturing a pharmaceutical composition for the treatment or prophylaxis of a disease, in particular of a hyper-proliferative and/or angiogenesis disorder, as a sole agent or in combination with other active ingredients.

Abstract: 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 compound of formula (I) wherein A, R1, R3, and R24 are described herein. The compounds are useful as inhibitors of potassium channel function and in the treatment of arrhythmia, IKur-associated disorders, and other disorders mediated by ion channel function.

Abstract: The present invention is directed to a compound of Formula (I) Formula (I) The invention also relates to pharmaceutical compositions comprising compounds of Formula (I) and methods comprising administering to a subject at least one compound selected from compounds of Formula (I) for treating diseases mediated by P2X7 receptor activity, such as rheumatoid arthritis, osteoarthritis, psoriasis, septic shock, allergic dermatitis, asthma, allergic asthma, mild to severe asthma, steroid resistant asthma, idiopathic pulmonary fibrosis, allergic rhinitis, chronic obstructive pulmonary disease; airway hyper-responsiveness, diseases of the nervous and neuro-immune system, acute and chronic pain states of neuropathic pain, inflammatory pain, spontaneous pain, opioid induced pain, diabetic neuropathy, postherpetic neuralgia, low back pain, chemotherapy-induced neuropathic pain, fibromyalgia, diseases involved with and without neuroinflammation of the central nervous system, mood disorders, major depression, major depress

Abstract: The present invention relates to compounds of general formula I wherein R1 is halogen, lower alkyl, lower alkoxy, lower alkyl substituted by halogen, lower alkoxy substituted by halogen or cyano; R2 is hydrogen, CF3 or lower alkyl; R3 is hydrogen, lower alkyl, lower alkenyl, lower alkinyl, heterocycloalkyl, lower alkyl substituted by cyano, cyano, benzyl substituted by halogen, 2-oxa-6-aza-spiro[3.3]hept-6-yl or is lower alkoxy substituted by halogen; X is —CH2— or —CH2—CH2—; or to a pharmaceutically acceptable acid addition salt, to a racemic mixture or to its corresponding enantiomer and/or optical isomers thereof.

Abstract: There are provided compounds comprising optionally substituted (FORMULA I) fused with one or two optionally substituted (FORMULA II), wherein A and E each independently represent —CH2—, —NH—, -0-, —S—, or —C(?O)— and B represents a bond, —CH2—, —NH—, -0-, —S—, or —C(?O)—, said compound having directly or indirectly attached thereto at least one acyl and/or oxime ester group. Such compounds are useful inter alias as photoinitiators.

Abstract: An opioid narcotics used for the treatment of moderate-to-severe pain that primarily exert their analgesic effects through ? receptors. Although, traditional ? agonists can cause undesired side effects, including tolerance, addition of ? antagonists can attenuate said side effects. The present invention includes 4a,9-dihydroxy-7a-(hydroxymethyl)-3-methyl-2,3,4,4a,5,6-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7(7aH)-one (UMB 425) a 5,14-bridged morphinan-based orvinol precursor, along with analogs of morphine, dihydromorphine, hydromorphone, codeine, dihydrocodeine, hydrocodone and ethylmorphine. Although UMB 425 lacks ?-specific motifs, conformationally sampled pharmacophore models for ? and ? receptors predict it to have efficacy similar to morphine at ? receptors and similar to naltrexone at ? receptors, due to the compound sampling conformations in which the hydroxyl moiety interacts with the receptors similar to orvinols.

Abstract: The present invention relates to novel compounds, pharmaceutical compositions containing such compounds and to their use in therapy.

Abstract: The present disclosure is generally directed to compounds which can inhibit AAK1 (adaptor associated kinase 1), compositions comprising such compounds, and methods for inhibiting AAK1.

Abstract: The invention relates to a compound of formula (I) wherein A and R1 to R4 are defined as in the description and in the claims. The compound of formula (I) can be used as a medicament.

Abstract: Isohexide monotriflate compounds and a method of preparing the same are described. The method involves reacting a mixture of an isohexide, a trifluoromethanesulfonate anhydride, and either 1) a nucleophilic base or 2) a combination of a non-nucleophilic base and a nucleophile. The isohexide monotriflate compounds can serve as precursor materials from which various derivative compounds can be synthesized.

Abstract: A process is described for the acid-catalyzed dehydration of a sugar alcohol, wherein the catalyst comprises a water-tolerant Lewis acid. In particular embodiments, the catalyst comprises a homogeneous water-tolerant Lewis acid, especially a homogeneous Lewis acid selected from the group consisting of bismuth (III) triflate, gallium (III) triflate, scandium (III) triflate, aluminum triflate, tin (II) triflate and indium (III) triflate. Such catalysts are effective for dehydrating both of sorbitol and the 1,4-sorbitan dehydration precursor of isosorbide, and bismuth (III) triflate particularly is beneficial for dehydrating mannitol to isomannide.

Abstract: Methods for preventing or treating retroviral infection, such as human immunodeficiency virus, in vivo utilize transcriptional inhibitory compounds. These include cortistatin A and analogs of the cortistatin family.

Abstract: A group of cyclic N-acyl O-amino phenol CBI derivatives were synthesized and shown to be pro-drugs, subject to reductive activation by cleavage of a N—O bond, effectively releasing the free drug in functional in vitro cellular assays for cytotoxic activity approaching the activity of the free drug, yet remain essentially stable to ex vivo DNA alkylation conditions. Assessment of the in vivo antitumor activity of a representative pro-drug indicates that a contemplated pro-drug approaches the potency and exceeds the efficacy of the free drug itself (CBI-indole2), indicating that the inactive pro-drugs not only effectively release the free drug in vivo, but that they offer additional advantages related to a controlled or targeted release in vivo.

Abstract: The present invention relates to sodium (2R,5S,13aR)-7,9-dioxo-10-((2,4,6-trifluorobenzyl)carbamoyl)-2,3,4,5,7,9,13,13a-octahydro-2,5-methanopyrido[1?,2?:4,5]pyrazino[2,1-b][1,3]oxazepin-8-olate Form I.

Abstract: The problem to be solved is to provide a method for efficiently producing compounds (1) and (1a) that are important intermediate compounds in the production of FXa inhibitors (X) and (X-a). The solutions thereto are a method for producing a compound represented by the formula (8d) using a stereoselective intramolecular cyclization reaction, and a method for producing a compound (1f) or a salt thereof, or a hydrate thereof, which is characterized by desulfonylation of the compound (8d). In each formula, R4a represents a C1-C6 alkyl group, a benzyl group, etc.

Abstract: In its many embodiments, the present invention provides certain C2-azaspiro substituted iminothiazine dioxide compounds. The novel compounds of the invention are useful as BACE inhibitors and/or for the treatment and prevention of various pathologies related thereto. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and use, including for the possible treatment of Alzheimer's disease, are also disclosed.

Abstract: Gold (I) hydroxide complexes of the form Z—Au—OH and digold complexes of the form Z—Au-(?OH)—Au—Z where groups Z are two electron donors are provided. The groups Z may be carbenes, for example nitrogen containing heterocyclic carbenes (NHCs), phosphines or phosphites. The complexes can be used as catalysts, for example in reactions such as hydration of nitriles, skeletal arrangement of enynes, alkoxycyclisation of enynes, alkyne hydration, the Meyer-Shuster reaction, 3,3? rearrangement of allylic acetates, cyclisation of propargylic acetates, Beckman rearrangements and hydroamination. The complexes can be used in medicine, for example in the treatment of cancer.

Abstract: The present invention relates to alkaline earth metal-complexed metal bisamides of the formula (I), to a process for preparation thereof and to the use thereof for metallation of aromatics, heteroaromatics, alkenes, alkynes and other organic compounds having activated C—H bonds.

Abstract: Described herein are compounds and compositions that modulate the activity of beta-lactamases. In some embodiments, the compounds described herein inhibit beta-lactamase. In certain embodiments, the compounds described herein are useful in the treatment of bacterial infections.

Abstract: This application relates to a process for making a pharmaceutically acceptable formulation of gadofosveset trisodium monohydrate, wherein the process uses no more than one chromatographic purification for removal of impurities.

Abstract: Provided are methods and intermediates for preparing diastereomerically pure phosphoramidate prodrugs of nucleosides of Formulas Ia and Ib: The compounds of Formula Ia and Ib are useful for the treatment Hepatitis C infections.

Abstract: The present invention relates to amino- or ammonium-containing sulfonic acid, phosphonic acid and carboxylic acid derivatives, in particular the compounds of formula 1, 2, 3, 4, 5 or 6, and their medical use, including their use in the treatment, prevention or amelioration of an inflammatory, autoimmune and/or allergic disorder.

Abstract: Preparation and in vitro and in vivo characterization of novel forms of active pharmaceutical ingredients, suitable for pharmaceutical compositions in drug delivery systems for humans.

Abstract: Provided is an oligonucleic acid analog which contains, as at least one structural unit thereof, a modified nucleic acid monomer compound which is a ring-open nucleoside having a cleaved carbon-carbon bond between the 2? and 3? positions and a substituent hydroxymethyl group at the 4? position. When used as siRNA, the oligonucleic acid analog exhibits superior biological stability and target gene expression inhibiting activity. The oligonucleic acid analog can be used in antisense methods, ribozyme methods, and decoy methods, etc., can be used as a nucleic acid aptamer, and can also be used as a nucleic acid probe or molecular beacon, etc., or in genetic diagnostics, etc.

Abstract: Provided is a pressure-cycling type of extraction device comprising: an extraction unit for accommodating and extracting an extraction target substance; a compression unit for increasing the pressure inside the extraction unit; and a decompression unit for decreasing the pressure inside the extraction unit; wherein the pressure inside the extraction unit is increased and decreased by alternately operating the compression unit and the decompression unit, and the extraction unit comprises a bubbling nozzle for supplying bubbles into the extraction target substance. Further provided is a pressure-cycling type of extraction method in which a compression process and a decompression process are carried out alternately, and compositions produced by the method. The extraction device and method allow low temperature extraction, permit outstanding extraction efficiency and can prevent colour changes, olfactory changes and thermal denaturation of the extraction target substance.

Abstract: A new class of molecules, C1—OH tributanoylated hexosamines, including, for example, GalNAc, GlcNAc and ManNAc, are demonstrated to increase cartilage-like tissue accumulation by IL-1?-stimulated chondrocytes. Furthermore, all three molecules reduced NFKB1 and I?B? driven gene expression, consistent with NF?B inhibitory properties of these analogs. GalNAc-a exposure produced the greatest ECM accumulation by IL-I?-stimulated chondrocytes. However, GalNAc-a exposure produced an opposite effect on MSC exposure, where a decrease in ECM accumulation was observed. These findings are in support of the function of NF?B signaling during limb development and growth plate chondrogenesis. The present invention shows the capability of this new class of hexosamine analogs as disease-modifying agents for treating cartilage damage.

Abstract: 5?-Deuterated nucleosides and nucleotides and modifications thereof are provided for use in medical therapies, including as antiviral, anti-tumor and anti-neoplastic agents. In one embodiment, compounds, methods and uses are provided for the treatment of hepatitis C, RSV, HSV and other viral diseases in a host, including a human.

Abstract: Disclosed herein are nucleotide analogs, methods of synthesizing nucleotide analogs and methods of treating diseases and/or conditions such as a HCV infection with one or more nucleotide analogs.

Abstract: The present invention relates to the synthesis of ent-progesterone and intermediates thereof.

Abstract: A synthetic polymeric molecule containing multiple subunits in which one or more of the subunits contains an amino acid side chain linked to a phosphate or modified phosphate group and is attached to an adjacent subunit by a phosphodiester or modified phosphodiester bond.

Abstract: The invention relates to a method for the selective purification and concentration of immunoglobulins or other proteins by means of an aqueous two-phase system using a centrifugal extractor.

Abstract: A pulse protein product having a protein content of at least about 50 wt % (N×6.25) d.b. is recovered in the processing of pulse protein source material to form pulse protein products wherein the pulse protein source is extracted in one embodiment with calcium salt solution. The resulting pulse protein solution is separated from the bulk of the residual pulse protein source and then the pulse protein solution is processed to remove finer residual solids, which are optionally washed and then dried to provide the pulse protein product. In another embodiment, the pulse protein source is extracted with water, the bulk of the residual protein source removed and the resulting pulse protein solution treated with calcium salt to precipitate phytic acid. The precipitated phytic acid and any finer residual solids remaining in solution after the initial separation step are removed from the pulse protein solution then optionally washed and dried to provide the pulse protein product.

Abstract: The present invention provides novel and improved protein purification processes which incorporate certain types of carbonaceous materials and result in effective and selective removal of certain undesirable impurities without adversely effecting the yield of the desired protein product.

Abstract: The invention described herein pertains to processes for preparing tubulysins and derivatives thereof. The invention described herein also pertains to processes for preparing tubulysin conjugates. The invention described herein also pertains to processes for preparing intermediates for preparing tubulysin conjugates. In one step, the alpha-thiazolyl alcohol is protected with triethylsilyl chloride in the presence of imidazole in an aprotic solvent.

Abstract: Disclosed herein are fibrillar molecular aggregates, which are morphologically and phenotypically similar to oligomers of aberrant proteins. The molecular aggregates, formed by self-assembly of small hydrophobic molecules, prevent the growth of microtubules. This unprecedented mechanism of “self-assembly to interfere with self-organization” allows inhibition of the growth of cancer cells.

Abstract: The methods and compositions described herein relate, in part, to the generation of a synthetic degradation system in E. coli that provides tunable control of the protein level of targeted genes by using components of the Mesoplasma florum tmRNA system. Provided herein are degradation tag variants that permit independent control of both the initial level and inducible degradation rate of attached proteins.

Abstract: The present invention provides oligopeptides, in particular, Ang-(1-7) derivatives, and methods for using and producing the same. In one particular embodiment, oligopeptides of the invention have higher blood-brain barrier penetration and/or in vivo half-life compared to the native Ang-(1-7), thereby allowing oligopeptides of the invention to be used in a wide variety of clinical applications including in treatment of cognitive dysfunction and/of impairment.

Abstract: Stem cells are mobilized from bone marrow by administering an amount of Phe-Pro-His-Phe-Asp-Leu-Ser-His-Gly-Ser-Ala-Gln-Val-Ser-Asp-Lys-Pro (SEQ ID NO: 2) or Phe-Ala-His-Phe-Asp-Leu-Ser-His-Gly-Ser-Ala-Gln-Val-Ser-Asp-Lys-Pro (SEQ ID NO: 3) effective to mobilize the stem cells. This is useful for promoting bodily tissue regeneration in a patient in need of tissue regeneration treatment. Alternatively, the mobilized stem cells can be collected for transplant.

Abstract: The present invention relates to novel matriptase inhibitors.

Abstract: Disclosed are methods of treating and/or inhibiting a viral infection in a subject. The methods include administering a therapeutically effective amount of heparin-binding peptide. Also disclosed herein are methods for blocking viral binding to a cell. Further disclosed are anti-viral compositions for administration to a subject infected with a virus. Administration of the anti-viral composition inhibits viral infection of the subject.