Abstract: The present invention provides a compound of formula I The compounds of formula I demonstrate properties as Smurf-1 inhibitors and are thus useful in the treatment of a range of disorders, particularly pulmonary arterial hypertension.

Abstract: The present invention provides a compound of formula I The compounds of formula I demonstrate properties as Smurf-1 inhibitors and are thus useful in the treatment of a range of disorders, particularly pulmonary arterial hypertension.

Abstract: The present invention is directed to compounds, tautomers and pharmaceutically acceptable salts of the compounds which are disclosed, wherein the compounds have the structure of Formula I, wherein the variables R1, R2 and R3 are as defined in the specification. Corresponding pharmaceutical compositions, methods of treatment, methods of synthesis, and intermediates are also disclosed.

Abstract: Disclosed are compounds of formula (I) which possess nematicidal properties wherein the structural elements have the meaning as indicated in the description.

Abstract: Antibacterial compounds of formula (I) are provided: as well as stereoisomers, pharmaceutically acceptable salts, esters, and prodrugs thereof; pharmaceutical compositions comprising such compounds; methods of treating bacterial infections by the administration of such compounds; and processes for the preparation of such compounds.

Abstract: The present invention is directed to a compound of Formula (I): wherein: n is an integer from 0-1; X is CH2 when n is 0, or X is CH2 or oxygen when n is 1; R1 is phenyl or pyridinyl, wherein the phenyl or pyridinyl is optionally substituted with from 1 to 4 substituents independently selected from halogen and alkyl; and R2 is phenyl, pyridinyl, pyrazinyl, pyradizinyl, pyrimidinyl, pyrrolyl, pyrazolyl, thiazolyl or thiophenyl, wherein the phenyl, pyridinyl, pyrazinyl, pyradizinyl, pyrimidinyl, pyrrolyl, pyrazolyl, thiazolyl or thiophenyl is optionally substituted with from 1 to 2 substituents independently selected from the group consisting of halogen, alkyl, hydroxy and alkoxy. The invention also relates to pharmaceutical compositions comprising compounds of Formula (I). Methods of making and using the compounds of Formula (I) are also within the scope of the invention.

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: Compounds of formula (I) that are capable of acting as purine receptor antagonists, pharmaceutical compositions including the compounds, and methods of making the compounds, are. disclosed. The compounds and compositions can be used in treating or preventing disorders related to purine receptor hyperfunctioning.

Abstract: Solid forms of chemical compounds that modulate kinase activity, including PI3 kinase activity, and compounds, pharmaceutical compositions, and methods of treatment of diseases and conditions associated with kinase activity, including PI3 kinase activity, are described herein. Also provided herein are processes for preparing compounds, polymorphic forms, cocrystals, and amorphous forms thereof, and pharmaceutical compositions thereof.

Abstract: The invention provides compounds of formula I: or a salt thereof as described herein. The invention also provided pharmaceutical compositions comprising a compound of formula I, processes for preparing compounds of formula I, intermediates useful for preparing compounds of formula I and therapeutic methods for treating the proliferation of the HIV virus, treating AIDS or delaying the onset of AIDS or ARC symptoms in a mammal using compounds of formula I.

Abstract: Various embodiments of the present invention are directed to compounds of the formula (I) or a pharmaceutically acceptable salt, polymorph, prodrug, solvate or clathrate thereof, wherein X1, X2, X3, R1, R2, R11, and n are defined herein. These compounds are useful as inhibitors of HIV-1 protease and, as a result, are useful in the treatment of HIV infection.

Abstract: The present invention is directed to compounds, tautomers and pharmaceutically acceptable salts of the compounds which are disclosed, wherein the compounds have the structure of Formula I, wherein the variables R1, R2, R3, R4 and X are as defined in the specification. Corresponding pharmaceutical compositions, methods of treatment, methods of synthesis, and intermediates are also disclosed.

Abstract: The present invention describes a new crystalline form of rifaximin, characterized in that it is a solvated form of rifaximin called rifaximin ?. The invention also describes a process for the preparation of rifaximin ?, a pharmaceutical composition comprising said rifaximin form, and its use for treating inflammations and infections.

Abstract: The present invention is directed to compounds, tautomers and pharmaceutically acceptable salts of the compounds which are disclosed, wherein the compounds have the structure of Formula I, and the variables R1, R2 and R3 are as defined in the specification. Corresponding pharmaceutical compositions, methods of treatment, methods of synthesis, and intermediates are also disclosed.

Abstract: Thiazoloquinolines and thiazolonaphthyridines with an alkoxy substituent at the 6, 7, 8, or 9-position, pharmaceutical compositions containing the compounds, intermediates, methods of making and methods of use of these compounds as immunomodulators, for inducing cytokine biosynthesis in animals and in the treatment of diseases including viral and neoplastic diseases are disclosed.

Abstract: Provided herein are myeloid cell leukemia 1 protein (Mcl-1) inhibitors, methods of their preparation, related pharmaceutical compositions, and methods of using the same. For example, provided herein are compounds of Formula I, and pharmaceutically acceptable salts thereof and pharmaceutical compositions containing the compounds. The compounds and compositions provided herein may be used, for example, in the treatment of diseases or conditions, such as cancer.

Abstract: Disclosed herein are antimicrobial compounds compositions, pharmaceutical compositions, the use and preparation thereof. Some embodiments relate to boronic acid derivatives and their use as therapeutic agents.

Abstract: The present invention describes chemical systems and methods for silylating heteroaromatic organic substrates using at least alkoxide base, preferably a potassium alkoxide base and at least one organodisilane and (b) at least one alkoxide base. Both methods and compositions for affecting these transformations are disclosed.

Abstract: The present invention is directed to a mild, efficient, and general direct C(sp)-H bond silylation. Various embodiments includes methods, each method comprising or consisting essentially of contacting at least one organic substrate comprising a terminal alkynyl C—H bond, with a mixture of at least one organosilane and an alkali metal hydroxide, alkali metal alkoxide, or alkali metal hydride under conditions sufficient to form a silylated terminal alkynyl moiety. The methods are operable in the presence or substantially absence of transition-metal compounds. The systems associated with these methods are also disclosed.

Abstract: Silicone containing reactive monomers with hydrophilic end-groups of formula I useful in the manufacture of biocompatible medical devices are disclosed, wherein R1 is H or CH3, a is 0 or 1, p is an integer from 1 to 6, q is an integer from 1 to 3 and for each q, the end groups R51, R52, R53 are independently an alkyl, alkyl ether, urethane, trimethylsiloxy group, or a substituted or non-substituted aromatic group and at least one of them has a hydrophilic group Z attached wherein said hydrophilic group Z is selected from the group of poly(ethylene glycol), poly(propylene glycol), poly(ethyl oxazoline), poly(methyl oxazoline), hyaluronic acid, or combinations thereof, preferably to the terminal end of R51, R52, R53, X is O or NR54, where R54 is H or a monovalent alkyl group with 1 to 4 carbons, n is an integer from 1 to 100, R2 and R3 is independently an alkyl, alkyl ether, trimethylsiloxy group, or a substituted or non-substituted aromatic group, preferred R2 and R3 include methyl, ethyl, trimethylsiloxy

Abstract: A method for preparation and polymerization of siloxane monomers of Formula I is presented. The synthesis includes the selective reaction between silanol containing unit and alkoxy containing units in the presence of basic catalyst. The siloxane monomers of the invention can be used for preparation of siloxane polymers with good flexibility and cracking threshold, and functional sites, useful for applications requiring low metal content in semiconductor industry.

Abstract: A polyorganosiloxane resin represented by the following general formula (5): (R3SiO1/2)1?(R2SiO2/2)m?(RSiO3/2)n?(SiO4/2)o? (5) wherein R is, independently of each other, a hydrogen atom or a monovalent hydrocarbon group having 1 to 18 carbon atoms, and optionally having an oxygen, halogen, nitrogen or sulfur atom; 1?, m? and o? are, independently of each other, an integer of from 0 to 10,000; n? is an integer of from 1 to 10,000; a total of 1?, m? and n? is from 2 to 30,000; and at least one R is a hydrogen atom and at least one R is an —OX group in the molecule, wherein X is an alkyl group having 1 to 10 carbon atoms or an alkoxyalkyl group having 2 to 10 carbon atoms; and at least one hydrogen atom and at least one —OX group bond to one and the same silicon atom.

Abstract: The present invention relates to organosilicon polymers containing benzoic acid esters in form of particles, process for their preparation, cosmetic or dermatological composition comprising them, as well as their use for protecting a human or animal living body from UV radiation.

Abstract: An organosilicon compound having diphenylethyl and methoxysilyl groups is more readily hydrolyzable than ethoxysilyl-containing organosilicon compounds and generates no hydrogen chloride on use.

Abstract: Universally usable process for reducing the chlorine content of organotetraphosphites.

Abstract: The invention relates to a universally applicable method for reducing the chlorine content of organomonophosphites using dimethylaminobutane or triethylamine.

Abstract: Embodiments of the present disclosure relate generally to novel achiral and chiral sulfur-, nitrogen- and phosphorus-containing ligands, designated as NNS-type, P(O)NS-type, PNS-type, SNNS-type, SNNP(O)-type, or SNNP-type polydentate ligands and transition metal complexes of these ligands, including iridium complexes having PNS-type and NNS-type ligands. The catalysts derived from these ligands and transition metal complexes may be used in a wide range of catalytic reactions, including hydrogenation and transfer hydrogenation of unsaturated organic compounds, dehydrogenation of alcohols and boranes, various dehydrogenative couplings, chemoselective hydrogenation of ?,?-unsaturated alcohols, and other catalytic transformations.

Abstract: Disclosed is a derivative of amphotericin B (AmB), denoted C2?epiAmB, with an improved therapeutic index over amphotericin B, pharmaceutical compositions comprising the AmB derivative, methods of making the AmB derivative and the pharmaceutical composition, and their use in methods of inhibiting growth of a yeast or fungus and treating a yeast or fungal infection. C2?epiAmB is an epimer of the parent compound. Specifically, C2?epiAmB differs from the parent compound at the CT stereogenic center on mycosamine. This difference in structure results in (i) retained capacity to bind ergosterol and inhibit growth of yeast, (ii) greatly reduced capacity to bind cholesterol, and (iii) essentially no toxicity to human cells.

Abstract: Gemcitabine analogs, including monophosphorylated analogs, are described herein and are suitable for use in pharmaceutical compositions, kits and treatment methods. The treatment methods include treatment of viral infections, including, but not limited to, treatment of Hepatitis C Virus, and uncontrolled cellular proliferation, including cancer, such as, but not limited to, non-small cell lung cancer, pancreatic cancer, bladder cancer, breast cancer, liver cancer, esophageal cancer and lymphoma.

Abstract: This invention provides methods for attaching a nucleic acid to a solid surface and for sequencing nucleic acid by detecting the identity of each nucleotide analogue after the nucleotide analogue is incorporated into a growing strand of DNA in a polymerase reaction. The invention also provides nucleotide analogues which comprise unique labels attached to the nucleotide analogue through a cleavable linker, and a cleavable chemical group to cap the —OH group at the 3?-position of the deoxyribose.

Abstract: This invention provides methods for attaching a nucleic acid to a solid surface and for sequencing nucleic acid by detecting the identity of each nucleotide analogue after the nucleotide analogue is incorporated into a growing strand of DNA in a polymerase reaction. The invention also provides nucleotide analogues which comprise unique labels attached to the nucleotide analogue through a cleavable linker, and a cleavable chemical group to cap the —OH group at the 3?-position of the deoxyribose.

Abstract: The invention is related to phosphorus substituted anti-viral inhibitory compounds, compositions containing such compounds, and therapeutic methods that include the administration of such compounds, as well as to processes and intermediates useful for preparing such compounds.

Abstract: 2? and/or 3? prodrugs of 1?, 2?, 3? or 4?-branchednucleosides, and their pharmaceutically acceptable salts and derivatives are described. These prodrugs are useful in the prevention and treatment of Flaviviridae infections, including HCV infection, and other related conditions. Compounds and compositions of the prodrugs of the present invention are described. Methods and uses are also provided that include the administration of an effective amount of the prodrugs of the present invention, or their pharmaceutically acceptable salts or derivatives. These drugs may optionally be administered in combination or alteration with further anti-viral agents to prevent or treat Flaviviridae infections and other related conditions.

Abstract: Described is a process for the preparation of monofluoromethylated organic biologically active compounds using monofluoromethylated reagents. Fluticasone Propionate and Fluticasone Furoate can be prepared using, for example, S-monofluoromethyl-S-phenyl-2,3,4,5-tetramethylphenylsulfonium tetrafluoroborate as monofluoromethylating reagent instead of bromofluoromethane.

Abstract: Methods and systems for making intermediates in the synthesis of onapristone are provided. Aspects include the photoconversion of onapristone synthesis intermediates using a narrow band frequency light source.

Abstract: Chemical entities that are novel compounds, pharmaceutical compositions and methods of treatment of cancer are described.

Abstract: The present invention provides novel stabilized crosslinked compounds having secondary structure motifs, libraries of these novel compounds, and methods for the synthesis of these compounds libraries thereof. The synthesis of these novel stabilized compounds involves (1) synthesizing a peptide from a selected number of natural or non-natural amino acids, wherein said peptide comprises at least two moieties capable of undergoing reaction to promote carbon-carbon bond formation; and (2) contacting said peptide with a reagent to generate at least one crosslinker and to effect stabilization of a secondary structure motif. The present invention, in a preferred embodiment, provides stabilized p53 donor helical peptides. Additionally, the present invention provides methods for disrupting the p53/MDM2 binding interaction comprising (1) providing a crosslinked stabilized ?-helical structure; and (2) contacting said crosslinked stabilized ?-helical structure with MDM2.

Abstract: Provided herein are antibacterial compounds, wherein the compounds in some embodiments have broad spectrum bioactivity. In various embodiments, the compounds act by inhibition of bacterial type 1 signal peptidase (SpsB), an essential protein in bacteria. Pharmaceutical compositions and methods for treatment using the compounds described herein are also provided.

Abstract: The present invention discloses compounds of Formula I or pharmaceutically acceptable salts, esters, or prodrugs thereof: which inhibit serine protease activity, particularly the activity of hepatitis C virus (HCV) NS3-NS4A protease. Consequently, the compounds of the present invention interfere with the life cycle of the hepatitis C virus and are also useful as antiviral agents. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from HCV infection. The invention also relates to methods of treating an HCV infection in a subject by administering a pharmaceutical composition comprising the compounds of the present invention.

Abstract: The present invention provides osteogenic peptides derived from the Cementum-derived attachment protein (HACD1/CAP) and another derived from the Cementum Protein 1 (CEMP1) and pharmaceutical compositions of these peptides for the prevention and treatment of osteopenia and osteoporosis. These peptides increase bone mineral density in an osteoporotic model and without in vivo side effects, demonstrating clinical effectiveness in the prevention and treatment of osteopenia and osteoporosis in vivo as well as bone repair and/or regeneration.

Abstract: Cyclic D,L-?-peptides were shown to have an anti-amyloid aggregation effect. The cyclic peptide (designated cyclic peptide-2) having the sequence [1JwHsK], had a drastic effect on amyloid aggregation. However, the linear equivalent of cyclic peptide-2 did not inhibit amyloid formation. Cyclic peptide 2 was also effective in reducing A?-induced toxicity in PC12 cells. According to embodiments of the invention, cyclic peptides may comprise between 6 or 8 amino acids. In an embodiment, half of the amino acid residues are in the D-formation, and the other half are in the L-formation. In an embodiment of the invention, the amino acids alternate between the D and L-formations.

Abstract: Disclosed are peptides which specifically bind to preselected pre-miRNA or pri-miRNA targets, methods of down-regulating EMT in a cell using such peptides, and methods of preparing such peptides. Also provided are therapeutic compositions comprising peptides that specifically bind a preselected cancer marker which is a peptide or which is a pre-miRNA or a pri-miRNA and methods of treatment using the same.

Abstract: Viral infection is a persistent cause of human disease. Fusion polypeptide systems target the genomes of viral infections, rendering the viruses incapacitated.

Abstract: Described herein are variants of alpha-hemolysin having at least one mutation selected from T12R, T12K, N17R, N17K or combinations of T12 and N17 mutations. The variants in some embodiments may further comprise H144A. The ?-hemolysin variants have a decreased time to thread.

Abstract: The present invention relates e.g. to methods of producing statins in transgenic, non-filamentous microorganisms such as Saccharomyces cerevisiae. In addition, the present invention relates to the transgenic, non-filamentous microorganisms as such as well as various uses of transmembrane statin efflux pump(s) originating from various filamentous fungi. Moreover, the present invention relates to the transferring the compactin, lovastatin or monacolin K gene cluster originating from non-filamentous fungi into easily fermentable microorganisms, followed by expression or overexpression of the efflux pump encoding genes in said microorganisms in order to increase the microorganisms resistance to statins which in turn allows for production of elevated concentrations of natural statins compared to statin-producing methods known in the art.

Abstract: The invention, in some aspects relates to compositions and methods for altering cell activity and function and the introduction and use of light-activated ion channels.

Abstract: The invention relates to modified antibiotic peptides, in particular derivatives of apidaecin and oncocin, preferably having increased stability, reduced immunoreaction, and improved pharmacokinetics. In the invention, the peptide antibiotics are reversibly protected by means of a linker having the polymer polyethylene glycol (PEG). The peptide linker contains a recognition sequence for trypsin-like serum proteases. In the apidaecin derivatives, the linker and the PEG are bonded to a side chain. In the serum, the linker is cut by serum proteases and PEG is separated off. The released peptide still contains remnants of the linker, which are still bonded to the amino group in the side chain. Astonishingly, said remaining remnants of the linker impair the activity of the antimicrobial peptide only a little or not at all.

Abstract: Aggregation is a major cause of the misbehavior of proteins. A system for modifying a protein to create a more stable variant is provided. The method involves identifying non-conserved hydrophobic amino acid residues on the surface of a protein, suitable for mutating to more hydrophilic residues (e.g., charged amino acids). Any number of residues on the surface may be changed to create a variant that is more soluble, resistant to aggregation, has a greater ability to re-fold, and/or is more stable under a variety of conditions. The invention also provides GFP, streptavidin, and GST variants with an increased theoretical net charge created by the inventive technology. Kits are also provided for carrying out such modifications on any protein of interest.

Abstract: The present invention provides methods and compositions for treating and/or preventing age related macular degeneration and other conditions involving macular degeneration, ocular neovascularization, or inflammation, including ocular inflammation. In some embodiments, the methods comprise administering an expression vector that delivers a secretable and cell penetrating Nrf2 to a subject in need thereof.

Abstract: The invention provides formulations and methods for ameliorating symptoms associated with metabolic disorders, such as cachexia, hypoglycemia, obesity, diabetes, and the like by administering Zn-?2-glycoproteins or a functional fragment thereof, alone or in combination with additional agents, such as ? adrenergin receptor agonists, ? adrenergin receptor antagonists, and/or glycemic control agents.