Abstract: Compounds of formula I defined herein are provided. Uses of these compounds for controlling invertebrate pests, protecting plant propagation material and providing an agricultural and a veterinary composition including the compounds are also described. Compounds for use as intermediate compounds in the preparation of compounds I are also described.

Abstract: Disclosed herein are novel GRK2 inhibitors and methods for their use in treating or preventing heart disease, such as cardiac failure, cardiac hypertrophy, and hypertension. In particular, disclosed herein are compounds of Formula (I) and pharmaceutically acceptable salt thereof: wherein the substituents are as described.

Abstract: The present invention relates to a compound of formula (I), a stereomeride, pharmaceutically acceptable salt, a solvate or an N-oxide thereof, a medicine composition comprising the compound, a method for preparing the compound, and a usage of the compound in treating diseases related to Hsp70. The diseases are preferably selected from tumors, neurodegenerative diseases, and allogeneic transplantation rejection and infection.

Abstract: The invention relates to normal or acidic salts of dasatinib and the hydrate and solvate forms thereof. More specifically the invention concerns: dasatinib cyclamic acid salt, dasatinib cyclamic acid (1:1) salt Form I, dasatinib cyclamic acid (1:1) salt Form II, dasatinib hydrogen bromide (1:2) salt, dasatinib methane sulfonic acid (1:2) salt, dasatinib p-toluenesulfonic acid (1:1) dihydrate salt, anhydrous dasatinib p-toluenesulfonic acid (1:1) salt Form I, anhydrous dasatinib p-toluenesulfonic acid (1:1) salt Form II, dasatinib p-toluenesulfonic acid (1:1) salt methanol solvate. Moreover the invention relates process for preparing dasatinib salts, pharmaceutical compositions comprising thereof and the use of dasatinib salts the treatment of cancer.

Abstract: Compounds having General Formula (I) or General Formula (II): in which R1 is chosen from C1 to C10 aliphatic or heteroaliphatic groups, optionally substituted with one or more aryl groups, substituted aryl groups, heteroaryl groups, substituted heteroaryl groups, or combination thereof; R2 is chosen from aromatic moieties, substituted aromatic moieties, heteroaromatic moieties substituted heteroaromatic moieties, and coumarin; R3 is chosen from —H, C1 to C10 aliphatic or heteroaliphatic groups, phenyl, or substituted phenyl, wherein the aliphatic or heteroaliphatic groups are optionally substituted with one or more phenyl groups, aryl groups, heteroaryl groups, substituted heteroaryl groups, or combination thereof, and wherein the aliphatic or heteroaliphatic groups are optionally bonded to R2 to form a ring; X is S or O; and Y is S or NH, may be used in pharmaceutical compositions that modify of biological signaling processes or as reagents for biological assays.

Abstract: A compound of formula (I) or a salt thereof wherein R1 represents a hydrogen atom, a methyl group or a ethyl group R2 represents a hydrogen atom or a fluorine atom R3 represents a hydrogen atom, a methyl group or an ethyl group.

Abstract: A method of preparing Compound (1) or a pharmaceutically acceptable salt thereof: comprises: (a) reacting Compound (X): or a pharmaceutically acceptable salt thereof with Compound (Y): in the presence of a palladium catalyst and a carbonate or phosphate base to form compound (Z): or a pharmaceutically acceptable salt thereof; and (b) deprotecting the Ts group of Compound (Z) to form Compound (1) or a pharmaceutically acceptable salt thereof.

Abstract: Provided herein are compounds of the General Formula I: and stereoisomers and pharmaceutically acceptable salts or solvates thereof, in which A, B, D, E, X1, X2, X3 and X4 have the meanings given in the specification, which are inhibitors of RET kinase and are useful in the treatment and prevention of diseases which can be treated with a RET kinase inhibitor, including diseases or disorders mediated by a RET kinase.

Abstract: The present invention provides compounds of formula I, compositions thereof, and methods of using the same for the inhibition of TYK2, and the treatment of TYK2-mediated disorders.

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: A process for preparing a diazabicyclooctane compound represented by the following formula (I): wherein A represents RcO—; B represents NH or NC1-6 alkyl; C represents a benzyl group; Rc represents a C1-6 alkyl group; A is substituted with one substituent Fn1, wherein Fn1 represents an azetidine group; the process including: (a) silylating the compound represented by the following formula (IV-c): wherein in the formula (IV-c), OBn represents benzyloxy, and (b) carrying out an intramolecular urea formation reaction.

Abstract: The present invention relates to substituted xanthines of general formula wherein R1 to R3 are as defined herein, the tautomers, the stereoisomers, the mixtures, the prodrugs thereof and the salts thereof which have valuable pharmacological properties, particularly an inhibiting effect on the activity of the enzyme dipeptidylpeptidase-IV (DPP-IV).

Abstract: The invention relates to Spirocyclic ether derivatives of pyrazolo[1,5-a]pyrimidine-3-carboxyamide of general formula (I) which are inhibitors of phosphodiesterase 2, useful in treating central nervous system diseases and other diseases. In addition, the invention relates to processes for preparing pharmaceutical compositions as well as processes for manufacture the compounds according to the invention.

Abstract: Disclosed are compounds of Formula (I); or a salt thereof; wherein Qi is (i) Cl, Br, I, —CN, —CH3, or —CF3; or (ii) pyrazole, triazole, or pyridinyl, each substituted with R1; Q2 is pyridinyl, indazolyl, isoquinolinyl, or benzo[d]imidazolyl substituted with R2 and R3; and R1, R2, and R3 are defined herein. Also disclosed are methods of using such compounds as modulators of PI3K, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing inflammatory and autoimmune diseases.

Abstract: A crystal form of JAK kinase inhibitor bisulfate and a preparation method thereof are provided. In particular, a type II crystal of (3aR,5s,6aS)—N-(3-methoxyl-1,2,4-thiadiazole-5-yl)-5-(methyl(7H-pyrrolo[2,3-d]pyrimidine-4-yl)amino)hexahydrocyclopenta[c]pyrrole-2(1H)-formamide bisulfate and a preparation method thereof are described. The preparation method includes steps of crystallizing any solid crystal form or amorphous compound of formula (I) in a single organic solvent or a mixed organic solvent to obtain a type II crystal form of the compound of formula (I). The type II crystal form of the compound of formula (I) obtained by the described methods has good crystal stability and chemical stability. In addition, the solvent used for crystallization has low toxicity and residue, which is better suited for use in clinical treatment.

Abstract: Crystals of a dispiropyrrolidine compound or a salt thereof which inhibits the action of Mdm2 are provided. The present invention provides crystals of (3?R,4?S,5?R)—N-[(3R,6S)-6-carbamoyltetrahydro-2H-pyran-3-yl]-6?-chloro-4?-(2-chloro-3-fluoropyridin-4-yl)-4,4-dimethyl-2?-oxo-1?,2?-dihydrodispiro[cyclohexane-1,2?-pyrrolidine-3?,3?-indole]-5?-carboxamide or a salt thereof which inhibits Mdm2 and has anti-tumor activity. The present invention also provides a medicament comprising the same.

Abstract: The present disclosure is concerned with certain pyrrolopyrimidine compounds that are capable of inhibiting certain protein kinases, and especially the leucine-rich repeat kinase 2 (LRRK2) protein. Compounds of the present disclosure can be used to treat a number of disorders caused by or associated with abnormal LRRK2 kinase activity. Compounds of the present disclosure can be used to treat disorders including neurodegenerative diseases such as Parkinson's disease; precancerous conditions and cancer; autoimmune disorders such as Crohn's disease, rheumatoid arthritis and psoriasis; and leprosy (Hansen's disease). This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

Abstract: The present disclosure generally provides compounds useful for treating cancer. In some aspects, the disclosure provides small-molecule cytotoxins that are chemically modified to include one or more moieties that include hydrophobic portions. In some embodiments, the disclosure provides small-molecule cytotoxins that are chemically modified with fatty acid-containing moieties. In some aspects, the disclosure provides compositions, such as pharmaceutical compositions, that include such modified small-molecule cytotoxins and a protein. In some embodiments, the protein is albumin or an albumin mimetic. Further, the disclosure provides various uses of these compounds and compositions.

Abstract: The present invention provides a crystal of 6-arylamino pyridone carboxamide compound and a preparation method thereof. The crystal is obtained by dissolving 6-(2-chloro-4-iodophenylamino)-N-(2-hydroxylethyoxyl)-5-methyl-4-oxo-4,5-dihydrofuro[3,2-c]pyridin-7-carboxamide in an aprotic polar solvent and adding a second solvent thereto. The crystallization method has the advantage of simple and convenient operations, and is beneficial to an industrial production. The resulting crystal has the advantage a high purity and good stability, and is benefit to the manufacture and storage of a medicament containing the same.

Abstract: The problem to be solved by the present invention is to provide a compound suitable for a pharmaceutical composition, specifically a pharmaceutically composition for treating nocturia. The inventors have assumed that inhibition of nocturnal activity of placental leucine aminopeptidase (P-LAP), i.e. aminopeptidase that cleaves AVP, would maintain and/or increase an endogenous AVP level to enhance the antidiuretic effect, which would contribute to a decreased number of nocturnal voids, and have extensively studied compounds which inhibit P-LAP. As a result, the inventors have found that (2R)-3-amino-2-(bi-cyclic pyridylmethyl)-2-hydroxy-propanoic acid derivatives have excellent P-LAP inhibitory activity. The inventors have evaluated antidiuretic effects in water-loaded rats and have found that the compounds increase endogenous AVP levels by inhibiting P-LAP and consequently reduce urine production.

Abstract: Drug formulations, methods and their use in treatment of diseases using formulations of pure di-acid salts of tetrandrine family members, especially d-tetrandrine di-hydrochloride, combined with a pharmaceutical diluent or carrier.

Abstract: The invention covers new bicyclic bridged [1,3]oksazepine derivatives of the general formula (I) and (II): which exhibit enhanced photochromic properties as compared with known spiropyrans and can be used as molecular photoswitches. The method of production of new compounds and intermediates for preparation thereof are disclosed.

Abstract: A method for acid-catalyzed acylation of an isohexide is described. The method involves a reaction of an isohexide and an excess of carboxylic acid in the presence of a Lewis acid or a Brnsted acid catalyst. One or more Lewis acid or Brnsted acid can facilitate conversion of isohexides to their corresponding mono and diesters with a pronounced greater regio-selectivity of exo-OH over endo-OH of the isohexide in the product. Particular catalytic acid species include zirconium chloride (ZrCl4) and phosphonic acid (H3PO3), which manifest a ratio of exo:endo regioselectivity of about 5.0?3:1 and about 4.00.3:1, respectively.

Abstract: This invention provides compounds having the structure which may be used for the treatment of tumors.

Abstract: K-Ras is the most frequently mutated oncogene in human cancer. Disclosed herein are compositions and methods for modulating K-Ras and treating cancer.

Abstract: Compounds of the formula I or II: wherein X, m, Ar, R1 and R2 are as defined herein. The subject compounds are useful for treatment of IRAK-mediated conditions.

Abstract: The present invention provides a substituted pyridine compound of the formula I or an agriculturally suitable salt or N-oxide thereof, wherein the variables in the formula I are defined as in the description. Substituted pyridine compounds of formula I are useful as herbicides.

Abstract: A heterocyclic derivative represented by formula (I), or a pharmaceutically acceptable salt or a stereoisomer thereof, which has an inhibitory effect on the activation of STAT3 protein, and is useful for the prevention or treatment of diseases associated with the activation of STAT3 protein.

Abstract: The present invention relates to substituted heterocyclic derivative compounds, compositions comprising said compounds, and the use of said compounds and compositions for epigenetic regulation by inhibition of bromodomain-mediated recognition of acetyl lysine regions of proteins, such as histones. Said compositions and methods are useful for the treatment of cancer and neoplastic disease.

Abstract: An ALK kinase inhibitor compound as represented by Formula I, pharmaceutical composition containing the compound, and preparation method and use thereof in the preparation of drugs serving as an ALK inhibitor for treating cancer.

Abstract: A method of preparing a crystalline zwitterionic zinc(II)-carboxylate compound includes the steps of preparing a mixture of zinc(II) ions and a first pyridyl ligand having three carboxylic acid moieties; subjecting the mixture to conditions under which a precipitate is formed; separating the precipitate; adding a solvent and optionally a second pyridyl ligand to the separated precipitate; subjecting the obtained mixture to conditions under which crystals of the zwitterionic zinc(II)-carboxylate compound are formed; and separating the crystals of the zwitterionic zinc(II)-carboxylate compound. Preferably but not exclusively, the crystalline zwitterionic zinc(II)-carboxylate compound essentially consists of at least one 1D coordination polymer.

Abstract: A reagent includes an element, formally in oxidation state zero, in complex with a hydride molecule and an incorporated ligand. The incorporated ligand typically has surface active properties. The reagent, termed a Ligated Anionic Element Reagent Complex, can be useful in synthesis of elemental nanoparticles. A method for synthesizing the aforementioned reagent includes a step of ball-milling a mixture containing an elemental powder, bulk hydride molecule, and bulk ligand. The components of the reagent, once complexed, have altered electronic structure and vibrational modes.

Abstract: The present invention is characterized in that racemic or optically active D- or L-?-glycerophosphoryl choline solids are prepared from liquid type racemic or optically active D- or L-?-glycerophosphoryl choline using an organic solvent. The present invention can produce solids at a high yield more easily through phase transformation rather than a method using a difference in solubility in a solvent, which is an existing method.

Abstract: This invention provides compounds, compositions and methods for modulating the expression of human p21 using RNA interference. The RNA interference molecules can be used in methods for preventing or treating diseases such as malignant tumor. Provided are a range of siRNA structures, having one or more nucleotides being modified or chemically-modified. Advantageous structures include siRNAs with 2?-deoxy nucleotides located in the seed region, as well as other nucleotide modifications.

Abstract: An organometallic compound represented by Formula 1: wherein in Formula 1, CY1, M, L, R1, R2, R3, R4, a1, a2, n1, and n2 are described in the specification.

Abstract: The present invention relates to the compounds of formula I, pharmaceutically acceptable salts, and solvates thereof: wherein the various substituents are as defined herein. The compounds, solvates and salts thereof of Formula I are effective as anti-cancer compounds.

Abstract: Provided are processes and intermediates for the syntheses of nucleosides of pyrrolo[1,2-f][1,2,4]triazinyl and imidazo[1,2-f][1,2,4]triazinyl heterocycles of Formula I.

Abstract: This invention provides compound having a structure of Formulas: Furthermore, methods and uses of such compounds for covalently bonding to a sugar acceptor, to form modified protein therapeutics having reduced enzymatic hydrolysis, improved biological stability or an improved pharmacokinetic property.

Abstract: The present invention relates to hamamelitannin analogues, pharmaceutical compositions comprising the same, and combinations thereof with anti-microbial agents such as antibiotics or disinfectants. It in particular relates to the use of the compounds, compositions and combinations according to this invention in human or veterinary medicine, more in particular for use in the prevention and/or treatment of bacterial infections, such as Staphylococcus aureus infections, in humans or animals.

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: Disclosed are steviol glycosides referred to as rebaudioside V and rebaudioside W. Also disclosed are methods for producing rebaudioside M (Reb M), rebausoside G (Reb G), rebaudioside KA (Reb KA), rebaudioside V (Reb V) and rebaudioside (Reb W).

Abstract: Compositions, methods, and systems are provided for nucleotide analogs comprising protein shields for improving enzyme photostability in single molecule real time sequencing. Nucleotide analogs of the invention have a protein shield between the dye moieties and nucleotide moieties of the analog. The nucleotide analogs have two avidin proteins connected by a central dye component, and each avidin protein is further connected to a nucleotide component. The protein can prevent the direct interaction of the dye moiety with the enzyme carrying out nucleotide synthesis preventing photodamage to the enzyme. The nucleotide analogs of the invention can have multiple dyes and multiple nucleotide moieties.

Abstract: Provided herein are 3,3-disubstituted 19-nor-steroidal compounds according to Formula (I): and pharmaceutical compositions thereof. Such compounds are contemplated useful for the prevention and treatment of a variety of CNS-related conditions, for example, treatment of sleep disorders, mood disorders, schizophrenia spectrum disorders, disorders of memory and/or cognition, movement disorders, personality disorders, autism spectrum disorders, pain, traumatic brain injury, vascular diseases, substance abuse disorders and/or withdrawal syndromes, tinnitus, status epilepticus.

Abstract: A method for separating a biological conjugate from an aggregate. The molecular weight of the biological conjugate ranges from about 10 kDa to about 1000 kDa. In one embodiment, the method comprises the steps of: (e) providing a mixture comprising the biological conjugate and the aggregate, wherein the biological conjugate has a molecular weight of from about 10 kDa to about 1000 kDa; (f) providing a chromatography column containing a gel, wherein the gel comprises at least one polysaccharide; (g) introducing the mixture of step (a) into the chromatography column; (h) recovering the biological conjugate from the column.

Abstract: Disclosed are methods of purifying a protein sample. More specifically, provide are methods of removing or reducing the amount of high molecular weight species and/or high mannose species from a protein sample using a mixed mode chromatography step and a hydrophobic interaction chromatography step.

Abstract: A method of reducing aggregate content in a preparation having a target protein includes contacting the preparation with an alkyl cation to form a mixture, and contacting the mixture with at least one functionalized solid to remove excess alkyl cation.

Abstract: The present invention relates to the field of molecular biochemistry and medicine, and in particular to ligands comprising modified amino acid residues, targeting the amyloid-? peptide associated with Alzheimer's disease for prevention of aggregation, neurotoxicity and use thereof as drugs for treatment of Alzheimer's disease.

Abstract: A novel and improved process for preparation of bortezomib mannitol ester is derived, which process avoids excessive use of solvents, involves convenient, industrially feasible and economical techniques, and provides improvements in purity over processes known in the art.

Abstract: The invention provides a molecule that inhibits or prevents an interaction between a Src family kinase and an androgen or estradiol receptor, for use in preventing or treating a non-cancerous condition in which an activity of AR and/or ER is a contributory factor in a subject, or for use in preventing or treating a cancerous condition in which an activity of AR and/or ER is a contributory factor in a subject who wishes to preserve fertility, or for use in preventing or treating a gynecological condition in which an activity of AR and/or ER is a contributory factor in a subject.

Abstract: The disclosed peptidomimetic macrocycles modulate the activity of MCL-1. Myeloid cell leukemia 1 (MCL-1) is a protein that inhibits cell death. Peptidomimetic macrocycles, pharmaceutical compositions, and methods disclosed herein can be used for the treatment of disease in which MCL-1 is over-expressed, such as cancer. In particular, MCL-1-modulating peptidomimetic macrocycles disclosed herein can be applied in the setting of resistance to BCL-2 family inhibitors, which is often engendered by MCL-1 over-expression or hyper-activation.