Abstract: Disclosed are negative allosteric modulators of the metabotropic glutamate receptor subtype 5 (mGluR5); synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating neurological and psychiatric disorders associated with glutamate dysfunction using the compounds and compositions. 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: Disclosed are compounds, pharmaceutical compositions containing those compounds, and uses of the compounds and compositions as modulators of CK1, CK1?1, CK1?2, CKl?3, CK2, Pim 1, Pim2, Pim3, the TGF? pathway, the Wnt pathway, the JAK/STAT pathway, the AKT pathway, and/or the mTOR pathway. Uses are also disclosed for the treatment or prevention of a range of therapeutic indications due at least in part to aberrant physiological activity of CK1, CK1?1, CK1?2, CKl?3, CK2, Pim 1, Pim2, Pim3, the TGF? pathway, the Wnt pathway, the JAK/STAT pathway, the AKT pathway, and/or the mTOR pathway.

Abstract: The presently described technology provides a novel class of prodrugs of quetiapine that can be synthesized by chemically conjugating fatty acids to quetiapine. Pharmaceutical compositions and methods of synthesizing conjugates of the present technology are also provided. Methods of treating patients with the compositions of the present technology are also provided.

Abstract: This invention relates to compounds (Formula (1)) that are agonists of the muscarinic M1 receptor and which are useful in the treatment of muscarinic M1 receptor mediated diseases. Also provided are pharmaceutical compositions containing the compounds and the therapeutic uses of the compounds. Compounds provided are of formula where R1-R5, X1, X2 and p are as defined herein.

Abstract: Compounds active on the receptor protein tyrosine kinases c-kit and/or c-fms are provided herewith. Also provided herewith are compositions useful for treatment of c-kit mediated diseases or conditions and/or c-fms-mediated diseases or conditions, and methods for the use thereof.

Abstract: Provided are a class of pyrazolone compounds and a use thereof. In particular, a compound represented by formula I is provided, wherein the definition of each variable group is as described in the description. The compounds of formula (I) have a direct AMPK-activating activity and can significantly promote the phosphorylation of AMPK and ACC of L6 myocytes and HepG2 cells in a dose-dependent manner.

Abstract: The present invention provides pharmaceutically active pyrrolo[2,3-d]pyrimidinyl and pyrrolo[2,3-d]pyridinyl acrylamides and analogues thereof. Such compounds are useful for inhibiting Janus Kinase (JAK). This invention also is directed to compositions comprising methods for making such compounds, and methods for treating and preventing conditions mediated by JAK.

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

Abstract: The present invention provides compounds useful as inhibitors of Ca2+/calmodulin-dependent protein kinase (CaMKII), compositions thereof, and methods of using the same.

Abstract: The present invention relates to pyrazolopyridine derivatives, which are useful as medicaments, pharmaceutical compositions comprising one or more of the pyrazolopyridine derivatives, and the use of one or more of the pyrazolopyridine derivatives in methods for treating and/or preventing a disease caused or mediated by a parasite of the family Trypanosomatidae.

Abstract: Inhibitors of Ras protein, methods to modulate the activity of Ras protein, and methods of treatment of disorders mediated by Ras protein are provided. A method for regulating activity of a K-Ras, H-Ras or N-Ras mutant protein with a compound is described. Disorders that can be treated include cancer, such as hematological cancer, pancreatic cancer, MYH associated polyposis, colorectal cancer, or lung cancer.

Abstract: In its many embodiments, the present invention provides certain C-6 spirocarbocyclic iminothiadiazine compounds, including compounds Formula (I) or a tautomer thereof, and pharmaceutically acceptable salts of said compounds and said tautomers, wherein R1A, R1B, R2, RA, ring A, RA, m, L1, RL, ring C, RC, and p are as defined herein. 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: The compounds of formula (I) are inhibitors of SSAO activity wherein V, W, X, Y, Z, R1 and R2 are as defined in the claims.

Abstract: The invention discloses a method for preparing Palbociclib (I). The preparation method comprises the steps of: causing a ring-closing reaction of 2-acetyl-2-butenoic acid methyl ester and malononitrile to occur in an alkaline condition to generate 1,4,5,6-tetrahydro-2-methoxyl-4-methyl-5-acetyl-6-oxy-3-pyridine carbonitrile (II); causing a substitution reaction of the intermediate(II) and halogenated cyclopentane(III) to occur under the effect of acid binding agent to generate N-cyclopentyl-1,4,5,6-tetrahydro-2-methoxyl-4-methyl-5-acetyl-6-oxy-3-pyridinecarbonitrile (IV); causing a condensation reaction of the intermediate(IV) and N-[5-(1-piperazinyl)-2-pyridinyl]guanidine (V) to occur to generate 6-acetyl-8-cyclopentyl-5,8-dihydro-5-methyl-2-[[5-(1-piperazinyl)-2-pyridinyl]amino]-pyrido[2,3-d]pyrimidin-7(6H)-one (VI); and causing a dehydrogenation reaction of the intermediate(VI) and sodium selenate to occur to prepare Palbociclib(I).

Abstract: This invention reveals the method for preparing Palbociclib (I). The preparation includes: produce the 6-acetyl-5-methyl-2-substituent-pyrido[2,3-d]pyrimidin-7(8H)-one (IV) through the ring-closure reaction by using accessible raw materials of 1-(4-amino-2-substituent-5-pyrimidinyl) ethanone (II) and acetylacetic ester (III); produce the 6-acetyl-8-cyclopentyl-5-methyl-2-substituent-pyrido[2,3-d]pyrimidin-7(8H)-one (VI) through the substitution reaction between the intermediate (IV) and the cyclopentane halide (V); prepare the Palbociclib (I) through the condensation and hydrolysis reactions between the intermediate (VI) and 4-(6-amino-3-pyridinyl)-1-piperazinecarboxylic acid 1,1-dimethylethyl ester (VII). This method for preparing Palbociclib (I) is characterized by easily available raw materials, concise process and economy and environmental protection, and it is suitable for industrialized production.

Abstract: The invention relates generally to pharmaceutical tablet compositions comprising fumaric acid and the compound (S)-2-(3?-(hydroxymethyl)-1-methyl-5-((5-(2-methyl-4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-yl)amino)-6-oxo-1,6-dihydro-[3,4?-bipyridin]-2?-yl)-7,7-dimethyl-2,3,4,6,7,8-hexahydro-1H-cyclopenta[4,5]pyrrolo[1,2-a]pyrazin-1-one free base that is an inhibitor of Bruton's tyrosine kinase. The invention further relates to amorphous solid dispersions comprising at least one polymer and the Bruton's kinase inhibitor free base compound. The invention further relates to crystalline mesylate salts, crystalline chloride salts and crystalline sulfate salts of the Bruton's kinase inhibitor free base compound. In some aspects, the crystalline salts are single polymorphs.

Abstract: A method for treating prostate cancer in a subject, comprising administering a therapeutically effective amount of at least one agent to the subject, wherein the agent is selected from: (a) a phenyl-substituted imidazole, or a pharmaceutically acceptable salt or ester thereof; or (b) a compound, or a pharmaceutically acceptable salt or ester thereof, having a formula I of: wherein R20 is an aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocycloalkyl, substituted heterocycloalkyl, alkoxy, aryloxy, a silyl-containing group, a boryl-containing group, a phosphine-containing group, amino, a thio-containing group, a seleno-containing group, halide, or a nitro-containing group; R21 is an alkanediyl or a substituted alkanediyl; a is 0 or 1; c is 0 or 1; X is C or S; R22 is a moiety that includes at least one divalent amino radical; and R23 is an aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocycloalkyl, substituted heterocycloalkyl, alkoxy, aryloxy, a silyl-containing

Abstract: The invention described herein relates generally to neuroactive compounds and compositions for the treatment psychotic disorders, methods for treating psychosis using these neuroactive compounds, and methods for screening for novel neuroactive compounds. Certain aspects are directed to a family of compounds called “finazines.” Certain aspects are directed to in vivo screening methods using high-through-put behavioral assays in zebrafish.

Abstract: Biologically active compounds that can be used as photosensitizers for diagnostic and therapeutic applications, particularly for PDT of cancer, infections and other hyperproliferative diseases, fluorescence diagnosis and PDT treatment of a non-tumorous indication such as arthritis, inflammatory diseases, viral or bacterial infections, dermatological, ophthalmological or urological disorders are provided as well as providing methods to obtain them in pharmaceutical quality. In addition, conjugates are provided in which these photosensitizers are attached to water-soluble polymers via cleavable linkers that can be cleaved in the body under specific conditions. Another embodiment consists of formulating the desired tetrapyrrole photosensitizer into a pharmaceutical formulation to be injected into the body avoiding undesirable effects like solubility problems or delayed pharmacokinetics of the tetrapyrrole systems.

Abstract: Compounds of formula I, including their salts, as well as compositions and methods of using the compounds are set forth. The compounds have activity against hepatitis C virus (HCV) and may be useful in treating those infected with HCV.

Abstract: Crystalline solid forms of methyl {(2S)-1-[(2S,5S)-2-(9-{2-[(2S,4S)-1-{(2R)-2-[(methoxycarbonyl)amino]-2-phenylacetyl}-4-(methoxymethyl)pyrrolidin-2-yl]-1H-imidazol-5-yl}-1,11-dihydroisochromeno[4?,3?:6,7]naphtho[1,2-d]imidazol-2-yl)-5-methylpyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl}carbamate (Compound I) were prepared and characterized in the solid state: Also provided are processes of manufacture and methods of using these crystalline forms.

Abstract: Disclosed are compounds that may be used to inhibit the action of fatty acid amide hydrolase (FAAH), monoacylglycerol lipase (MAGL) or dual FAAH/MAGL.

Abstract: The present invention relates to inhibitors of IRAK4 of Formula I and provides compositions comprising such inhibitors, as well as methods therewith for treating IRAK4-mediated or -associated conditions or diseases.

Abstract: Compounds of formula (II): wherein R1, R2, R5 and R13 are described herein, or a stereoisomer, enantiomer or tautomer thereof or mixtures thereof, or a pharmaceutically acceptable salt or solvate thereof, are described herein, as well as other compounds. These compounds have activity as SHIP1 modulators, and thus may be useful in treating a variety of diseases, disorders or conditions that would benefit from SHIP1 modulation. Compositions comprising a compound of the invention are also disclosed, as are methods of SHIP1 modulation by administration of such compounds to an animal in need thereof.

Abstract: The present invention relates to novel indanyl urea derivatives, their pharmaceutically acceptable salts, and their isomers, stereoisomers, atropisomers, conformers, tautomers, polymorphs, hydrates and solvates. The present invention also encompasses process for preparing novel compounds and pharmaceutical composition of said compounds. The invention further relates to the use of the compounds for the preparation of medicament for use as pharmaceuticals.

Abstract: The present disclosure provides compounds and methods for inhibiting the interaction of menin with its upstream or downstream signaling molecules including but not limited to MLL1, MLL2 and MLL-fusion oncoproteins. Compounds of the disclosure may be used in methods for the treatment of a wide variety of cancers and other diseases associated with one or more of MLL1, MLL2, MLL fusion proteins, and menin.

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: The present invention relates to novel aminoisoxazoline compounds, and pharmaceutical compositions of the same, that are suitable as agonists or partial agonists of ?7-nAChR, and methods of preparing these compounds and compositions, and the use of these compounds and compositions in methods of maintaining, treating and/or improving cognitive function. In particular, methods of administering the compound or composition to a patient in need thereof, for example a patient with a cognitive deficiency and/or a desire to enhance cognitive function, that may derive a benefit therefrom.

Abstract: The present invention encompasses compounds of formula (I) wherein the groups R1 to R7, A, V, W, X, Y, n, r and q are defined in claim 1, their use as inhibitors of MDM2-p53 interaction, pharmaceutical compositions which contain compounds of this kind, their use as medicaments, especially as agents for treatment and/or prevention of oncological diseases, and synthetic intermediates.

Abstract: The present invention provides thiazole compounds of Formula I wherein W, Y, R0, R2, R4, R5, R6, R7, X1, X2, X3 and X4 are as defined herein, or a stereoisomer, tautomer, pharmaceutically acceptable salt, prodrug ester or solvate form thereof, wherein all of the variables are as defined herein. These compounds are inhibitors of platelet aggregation and thus can be used as medicaments for treating or preventing thromboembolic disorders.

Abstract: The present invention provides compounds of Formula (I): wherein A and R1 are each as defined in the specification, and compositions comprising any of such novel compounds. These compounds are myeloperoxidase (MPO) inhibitors and/or eosinophil peroxidase (EPX) inhibitors, which may be used as medicaments.

Abstract: Pyridine complex of zirconium having general formula (I): Said pyridine complex of zirconium having general formula (I) may advantageously be used in a catalytic system for the (co)polymerization of conjugated dienes.

Abstract: Disclosed are an o-phenyl chalcone compounds and preparation methods and uses thereof. The o-phenyl chalcone compounds are capable of inhibiting the aggregation of microtubules in tumor cells and influencing the mitosis of the cells, and has a high antitumor activity. The compounds also have inhibitory activity against proliferation on various tumor cells, such as a human ovary cancer cell A2780, a human colon cancer cell HCT8, a human breast cancer cell MCF7, a human lung cancer cell A549, a human colon cancer cell SW480, a human nasopharyngeal carcinoma cell CNE2, a human liver cancer cell HepG2 and the like at nanomole concentrations.

Abstract: The present invention generally relates to processes for the enzymatic production of a phosphinothricin product or precursor thereof from a nitrile-containing substrate.

Abstract: The present invention relates to novel biguanide derivatives including their pharmaceutically acceptable salts. The invention also relates processes for the preparation of, intermediates used in the preparation of, pharmaceutical compositions containing and the uses of such compounds in treating disorders such as diabetes.

Abstract: The present invention encompasses compounds and methods for treating urinary tract infections.

Abstract: The present invention relates to fluorescent dyes in general. The present invention provides a wide range of fluorescent dyes and kits containing the same, which are applicable for labeling a variety of biomolecules, cells and microorganisms. The present invention also provides various methods of using the fluorescent dyes for research and development, forensic identification, environmental studies, diagnosis, prognosis, and/or treatment of disease conditions.

Abstract: Disclosed are a compound represented by formula (I) and a pharmaceutically acceptable salt thereof, wherein R1, R2, R3, R4, R5, W, n are defined as in the present application.

Abstract: The present invention relates to a process for the synthesis of Sofosbuvir.

Abstract: Compounds are provided according to Formula (I) and pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof; wherein X, Y, R1, R2a, R2b, R4a, R4b, R5a, R5b, R6a, R6b, R7, and R8 are as defined herein. Compounds of the present invention are contemplated useful for the prevention and treatment of a variety of conditions.

Abstract: Described herein are steroids of Formula (I): and pharmaceutically acceptable salts thereof; wherein R1, R2a, R2b, R3, R4, R5a, R5b, R6, and Z are as defined herein. 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, convulsive 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, and tinnitus.

Abstract: The invention discloses a polypeptide capable of binding immunoglobulins or immunoglobulin-containing proteins, which polypeptide comprises six or more domains of protein Z or the C domain of protein A or a functional variant thereof. It also discloses separation matrices comprising the polypeptide and methods of using the separation matrices for separation of immunoglobulins or immunoglobulin-containing proteins.

Abstract: Compounds having cytotoxic and/or anti-mitotic activity are disclosed. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed. Also disclosed are compositions having the structure: (T)-(L)-(D), wherein (T) is a targeting moiety, (L) is an optional linker, and (D) is a compound having cytotoxic and/or anti-mitotic activity.

Abstract: The present invention relates to the field of wood rosin and resin acid derivatives and more particularly to abietane-type diterpenoids as well as different uses thereof. Furthermore, the present invention relates to methods of coating surfaces, preventing, reducing or inhibiting bacterial biofilm formation, and treating or preventing disorders caused by microbial growth and viability as well as bacterial colonization.

Abstract: A method for enhancing, by at least 10 fold, the antibacterial activity of an antisense oligonucleotide composed of morpholino subunits linked by phosphorus-containing intersubunit linkages. The method includes one or both of: conjugating an arginine-rich carrier to a 3? or 5? end of the oligonucleotide and modifying the oligonucleotide to contain 20%-50% intersubunit linkages that are positively charged at physiological pH. Also disclosed is an antisense oligonucleotide having enhanced antibacterial activity by virtue of one or both modifications.

Abstract: A peptide comprising an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, according to the present invention, shows proliferation and differentiation promotion of osteoblast and proliferation and activation promotion of periodontal ligament fibroblast. A peptide, according to the present invention, increases BMP signaling such as SMAD1/5/8 phosphorylation and increases the growth of osteoblast and the expression of a differentiation marker such as COL1A1, BSP and ALP, thereby ultimately showing osteoblast activation. A peptide, according to the present invention, promotes the growth of periodontal ligament fibroblast by means of PI3K and Akt phosphorylation and increases the expression of an activation marker such as COL1A1 and DSPP, thereby ultimately showing periodontal tissue regeneration activation. Provided are a composition for preventing or treating bone diseases and a composition for preventing or treating periodontal diseases, the compositions comprising the aforementioned peptide.

Abstract: Compounds and compositions are disclosed in which a quaternized drug unit is linked to a targeting ligand unit from which a tertiary amine-containing drug is released at the targeted site of action. Methods for treating diseases characterized by the targeted abnormal cells, such as cancer or an autoimmune disease using the compounds and compositions of the invention are also disclosed.

Abstract: Compounds comprising peptides capable of binding C3 protein and inhibiting complement activation are disclosed. The compounds comprise compstatin analogs in which the N-terminus contains an added or substituted component that improves (1) the peptide's binding affinity to C3 or its fragments, (2) the peptide's solubility in aqueous liquids, (3) the peptide's plasma stability, (4) the peptide's in vivo retention and/or (5) the peptide's bioavailability, as compared with an unmodified compstatin peptide under equivalent conditions. Pharmaceutical compositions and methods of using the compounds are also disclosed.

Abstract: Described herein are anti-microbial peptides having enhanced activity and transport.

Abstract: Occidiofungin is a cyclic nonribosomally synthesized antifungal peptide with submicromolar activity. This invention is directed to compositions enriched for particular occidiofungin diastereomers/conformers, methods of making compositions enriched for particular diastereomers/conformers and microorganisms suitable for producing enriched compositions of particular diastereomers/conformers. Methods of treating fungal infections or plants infected by fungi are also provided.