Abstract: The invention described herein pertains to processes for preparing tubulysin derivatives, conjugates of tubulysins, and intermediates therefore. In one illustrative embodiment of the invention, processes for derivatives or analogs of natural tubulysins including compounds of formula (T). In another embodiment, vitamin receptor binding conjugates of tubulysins are described. The processes include one or more steps described herein. In another embodiment, a process is described for preparing a compound of formula B, wherein R5 and R6 are as described in the various embodiments herein, such as each being independently selected from optionally substituted alkyl or optionally substituted cycloalkyl; and R8 is C1-C6 n-alkyl; wherein the process comprises the step of treating a compound of formula A with a silylating agent, such as triethylsilyl chloride, and a base, such as imidazole in an aprotic solvent.

Abstract: Compounds having the following formula I: or a stereoisomer or pharmaceutically-acceptable salt thereof, where R1, R2, R3, R4, and R5 are as defined herein, are useful in the modulation of IL-12, IL-23 and/or IFNa, by acting on Tyk-2 to cause signal transduction inhibition.

Abstract: Compounds of Formula I are useful inhibitors of tankyrase. Compounds of Formula I have the following structure: where the definitions of the variables are provided herein.

Abstract: The invention relates to antibacterial compounds of formula I wherein one or two of U, V, W, and X represent N, the rest represent CH or, in the case of X, may also represent CRa wherein Ra is fluorine; R1 represents alkoxy, halogen or cyano; R2 represents H, CH2OH, CH2N3, CH2NH2, alkylcarbonylaminomethyl or triazol-1-ylmethyl; R3 represents H, or, when n is 1, R3 may also represent OH, NH2, NHCOR6 or triazol-1-yl; A represents CR4; K represents O, NH, OCH2, NHCO, NHCH2, CH2NH, CH2CH2, CH?CH, CHOHCHOH or CHR5; R4 represents H or together with R5 forms a bond, or also R4 can represent OH when K is not O, NH, OCH2 or NHCO; R5 represents OH or together with R4 forms a bond; R6 represents alkyl; m is 0 or 1 and n is 0 or 1; and G is as defined in the description; and to salts of such compounds.

Abstract: Provided herein are substituted triazolopyrazine phosphodiesterase inhibitors, and pharmaceutical compositions thereof, useful for the treatment of, for example, central nervous system and metabolic diseases and disorder.

Abstract: Compounds of Formula I, including pharmaceutically acceptable salts thereof: formula (I): wherein A is selected from the group consisting of: formula (II) and wherein Z is selected from the group consisting of: formula (III): and. are useful as HIV attachment inhibitors.

Abstract: D-amino acid oxidase (DAAO) inhibitors and methods of their use, either alone or in combination with D-serine or D-alanine, to facilitate allosteric activation of NMDA receptor-mediated neurotransmission and methods of their use as therapeutic agents for treating a subject afflicted with one or more cognitive-disorders, such as schizophrenia, including subjects suffering from negative symptoms and cognitive impairments, post-traumatic stress disorder (PTSD), or pain, are disclosed.

Abstract: A compound is disclosed that has a formula represented by the following: This compound may be prepared as a pharmaceutical composition, and may be used for the prevention and treatment of a variety of conditions in mammals including humans, including by way of non-limiting example, inflammatory conditions, autoimmune diseases, proliferative diseases, transplantation rejection, diseases involving impairment of cartilage turnover, congenital cartilage malformations, and/or diseases associated with hypersecretion of IL6.

Abstract: The present invention provides a compound of formula I: a method for manufacturing the compounds of the invention, and its therapeutic uses. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.

Abstract: Compounds and compositions for treating disorders related to TRPA1 are described herein.

Abstract: Disclosed is a pharmaceutical composition including a bicyclic pyridinol derivative as an active ingredient for preventing or treating diseases caused by angiogenesis. The bicyclic pyridinol derivative expressed by Chemical Formula 1 can be effectively used as a drug for preventing and treating diseases caused by angiogenesis since it inhibits neovascularization in a chorioallantoic membrane model.

Abstract: The present invention relates to a compound having the general formula (V), optionally in the form of a pharmaceutically acceptable salt, solvate, polymorph, codrug, cocrystal, prodrug, tautomer, racemate, enantiomer, or diastereomer or mixture thereof, which are useful in treating, ameliorating or preventing a viral disease. Furthermore, specific combination therapies are disclosed.

Abstract: A novel process for the preparation of imidazo[1,2-a]pyridine compounds of the formula wherein R1 is C1-4-alkoxy or NR4R5 wherein R4 and R5 are independently hydrogen or C1-4-alkyl or R4 and R5, together with the nitrogen atom to which they are attached, form a saturated 4- to 6-membered heterocyclic ring which may contain one further heteroatom selected from nitrogen or oxygen; R2 is C1-4-alkyl, C1-4-alkoxycarbonyl, halogen, phenyl which is optionally substituted with C1-4-alkyl, C1-4-alkoxy or halogen or is NR4R5 wherein R4 and R5 are independently hydrogen or C1-4-alkyl or R4 and R5, together with the nitrogen atom to which they are attached, form a saturated 4- to 6-membered heterocyclic ring which may contain one further heteroatom selected from nitrogen or oxygen; R3 is C1-4-alkyl and X is nitrogen or CH is described.

Abstract: The present invention provides compounds of formula 1 as potential phosphodiesterase3 (PDE3) inhibitory agents and a process for the preparation thereof. The derivatives of formula 1 can be employed as therapeutics in human and veterinary medicine, where they can be used, for the treatment and prophylaxis of the following diseases: heart failure, dilated cardiomyopathy, platelet inhibitors, cancer and obstructive pulmonary diseases.

Abstract: New bicyclic compounds, their preparation, and their use as antibacterial agents, either alone or in combination with an antibiotic for the treatment of infections caused by ?-lactamase-producing pathogenic bacteria, are described.

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: Methods for regulating cancer cell growth and survival, inhibiting cancer cell growth, promoting cancer cell death, and/or treating a cancer make use of antagonists of a type I BMP receptor. In some embodiments the cancer is a lung cancer and the cancer cell is a lung cancer cell.

Abstract: Provided herein are methods for treating or preventing chronic lymphocytic leukemia, comprising administering an effective amount of a Dihydropyrazino-Pyrazine Compound to a patient having chronic lymphocytic leukemia.

Abstract: 4-alkoxy/aralkoxy-5-substituted-pyrrolopyrimidine compounds, pharmaceutically acceptable salts, solvates and pharmaceutical compositions of compounds embraced by Formula (I), provide a therapeutic benefit to subjects with disease conditions, especially cancer, wherein R1 and R2 are as defined in the detailed description.

Abstract: Methods of inhibiting kinases using kinase inhibitors having olefin moieties are disclosed.

Abstract: The present invention relates to compounds formula (I): and to salts thereof, wherein R1-R4 and A have any of the values defined in the specification, and compositions and uses thereof. The compounds are useful as inhibitors of histone demethylases, such as KDM5. Also included are pharmaceutically acceptable compositions comprising the compounds of the present invention and methods of using said compositions in the treatment of various disorders.

Abstract: Provided herein, inter alia, are methods and compositions for modulating TLR-4.

Abstract: The present invention provides compounds of Formula (I) as M1 receptor positive allosteric modulators for the treatment of diseases mediated by the muscarinic M1 mediator.

Abstract: Organic photovoltaic (OPV) devices are disclosed. An exemplary device has first and second electrodes and an organic, photovoltaically active zone located between the first and second electrodes. The photovoltaically active zone includes an organic electron-donor material and an organic electron-acceptor material. The electron-donor material includes one or more trivalent- or tetravalent-metal phthalocyanines with alkylchalcogenide ring substituents, and is soluble in at least one organic solvent. This solubility facilitates liquid-processability of the donor material, including formation of thin-films, on an unlimited scale to form planar and bulk heterojunctions in organic OPVs. These donor materials are photovoltaically active in both visible and near-IR wavelengths of light, enabling more of the solar spectrum, for example, to be applied to producing electricity. Also disclosed are methods for producing the metalated phthalocyanines and actual devices.

Abstract: A stable micronized monoclinic form of asenapine maleate is described, which comprises 5% by weight or less of orthorhombic form or any other crystalline form of asenapine maleate, wherein the asenapine maleate has a particle size distribution characterized by a d90 equal to or below 40 ?m. Processes for preparing the stable micronized monoclinic form of asenapine maleate are also described. Formula (I).

Abstract: The present invention provides an aromatic ring compound having a melanin-concentrating hormone receptor antagonistic action and useful as an agent for the prophylaxis or treatment of obesity and the like. The present invention relates to a compound represented by the formula wherein each symbol as defined in the specification, or a salt thereof.

Abstract: Novel rapamycin analogues and methods for their production with FKBP and/or MIP inhibitory activity with reduced mTOR inhibitory activity with therapeutic potential e.g. as bacterial virulence inhibitors.

Abstract: Provided are Icotinib maleate (the compound of Formula I) and polymorph forms thereof, and methods of preparing and using them.

Abstract: Compounds of Formula (I) wherein R1, R2, R3A, R3B, Y, Z1 and Z2 are defined herein, are useful for the treatment of cytomegalovirus disease and/or infection.

Abstract: The present invention provides compounds of formula (I), and pharmaceutical compositions thereof.

Abstract: The present invention relates to a method for preparing anhydrous sugar alcohol, and more particularly, to a cheap and highly efficient method for preparing anhydrous sugar alcohol having a high final purity of at least 99%, and having good ion content, pH, conductivity, and color properties. According to the method, a hydrogenated sugar is dehydrated so as to be transformed into anhydrous sugar alcohol, and a series of processes including distillation, crystallization, decoloration, and ion exchange resin treatment are conducted.

Abstract: Disclosed herein are monomers formed by reacting a sugar derived compound(s) comprising a lactone and two hydroxyls with a compound(s) comprising an isocyanate and an acrylate or methacrylate. Polymers formed from such monomers, and articles formed from the polymers are also disclosed.

Abstract: The present invention relates to novel tacrolimus analogs, a composition for the prevention or treatment of neurological diseases or immune hypersensitivity disorders comprising the same, a method for preventing or treating neurological diseases or immune hypersensitivity disorders comprising administering the analogs to a subject, a method for preparing the analogs using an isolated modified Streptomyces sp. strain wherein the activity of one or more enzymes selected from the group consisting of TcsA, TcsB, TcsC and TcsD is reduced; and the isolated modified Streptomyces sp. strain for prepare the analogs.

Abstract: The invention relates to methods of treating diseases including but not limited to, cancer, non-cancer proliferative disease, sepsis, autoimmune disease, viral infaction, atheroscleosis, Type 1 or 2 diabetes, obesity, inflammatory disease, or Myc-depenent disorder including by modulating biological processes by the inhibition of PI3 kinase and/or bromodomain protein binding to substrates composing the administration of a compound(s) of Formula I-IX (or pharmaceutically acceptable salts thereof) as defined herein.

Abstract: The present disclosure relates generally to thienopyrimidine and thienopyridine compounds and methods of use thereof. In particular embodiments, the present disclosure provides compositions comprising thienopyrimidine and thienopyridine compounds of Formula 4b: and methods of use to inhibit the interaction of menin with MLL1, MLL2 and MLL-fusion oncoproteins.

Abstract: The present disclosure relates generally to thienopyrimidine and thienopyridine compounds and methods of use thereof. In particular embodiments, the present disclosure provides compositions comprising thienopyrimidine and thienopyridine compounds of Formula 2: and methods of use to inhibit the interaction of menin with MLL1, MLL2 and MLL-fusion oncoproteins.

Abstract: The present invention provides a pyrone derivative and a pyridone derivative, which are novel intermediates for synthesizing an anti-influenza drug, a method of producing the same, and a method of using the same.

Abstract: The present application relates to therapeutic organic compounds, compositions comprising an effective amount of a therapeutic organic compound; and methods for treating and preventing disease comprising administering and effective amount of a therapeutic organic compound to a subject in need thereof.

Abstract: Pyridone and aza-pyridone compounds of Formula I are provided, including stereoisomers, tautomers, and pharmaceutically acceptable salts thereof, useful for inhibiting Btk kinase, and for treating immune disorders such as inflammation mediated by Btk kinase. Methods of using compounds of Formula I for in vitro, in situ, and in vivo diagnosis, and treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed.

Abstract: The present application relates to novel substituted fused pyrimidines and triazines, to processes for their preparation, to their use alone or in combinations for the treatment and/or prophylaxis of diseases, and to their use for producing medicaments for the treatment and/or prophylaxis of diseases, in particular for the treatment and/or prophylaxis of cardiovascular disorders.

Abstract: The present invention provides improved processes for the preparation of Bortezomib, tert -butyl[1-({(1S)-3-methyl-1-[(3aS,4S,6S,7aS)-3a,5,5-trimethylhexahydro-4,6-methano-1,3,2-benzodioxaborol-2-yl]butyl}amino)-1-oxo-3-phenylpropan-2-yl]carbamate of formula (IV) and N-{(1S)-3-methyl-1-[(3aS,4S,6S,7aS)-3a,5,5-trimethylhexahydro-4,6-methano-1,3,2-benzodioxaborol-2-yl]butyl} phenylalanine of formula (V). Compound (IV) is prepared by coupling (1R)-3-methyl-1-[(3aS,4S,6S,7aR)-3a,5,5-trimethyl-hexahydro-4,6-methano-1,3,2-benzodioxaborol-2-yl]butan-1-amine of formula (II) or its salt with N-(tert-butoxycarbonyl)-L -phenylalanine of formula (III) in a first solvent in the presence of a first coupling agent and a first base, wherein the coupling process does not comprise solvent exchange. Compound (V) is prepared by deprotecting compound (IV) using an alcoholic solution of an inorganic acid.

Abstract: The present invention relates to a process to prepare alkylaluminoxanes by reaction of alkylaluminium with a substituted allylic alcohol of the formula wherein each R1 and R2 independently are an aliphatic or aromatic hydrocarbon group, and R3, R4, and R5 each independently may be the same hydrocarbon group as R1 and R2 or a hydrogen atom in the presence of an inert organic solvent. Additionally, it relates to the alkylaluminoxanes obtainable by the above process and their use.

Abstract: The invention provides methods for cyclizing poly-yne compounds under mild conditions to provide cyclic compounds.

Abstract: The invention relates to novel silane compounds corresponding to the following formula (I): A-E-X??(I) in which: X represents a silylated group which makes possible the covalent attachment of the silane compound to the hydroxyl or hydride functional groups of a support; E represents an organic spacer group; A represents a group capable of releasing an —OH functional group by acid hydrolysis, the said —OH functional group, after the said hydrolysis, being covalently bonded to E. Use of these silane compounds for functionalizing solid supports and for immobilizing biological molecules on these supports.

Abstract: The invention relates to compounds of use as targeted cytotoxic agents and methods of use thereof. In particular, the invention relates to prodrugs that are substantially resistant to human AKR1C3 enzyme metabolism, methods of cell ablation using said compounds and methods of treatment of cancer and other hyperproliferative disorders using said compounds.

Abstract: Cidofovir is obtained in different forms, including amorphous cidofovir, crystalline anhydrous cidofovir, crystalline cidofovir monohydrate, and crystalline cidofovir dihydrate, including various polymorphs.

Abstract: The present invention relates to azine metal phosphates, compositions containing the same, a process for preparing the same and their use as flame retardants. Typical representatives are (A-H)(+)[MtPO4](+).2H2O and (Mel-H)(+)[AlP2O7](+) (where A=melamine or guanidine, Mel=melamine and Mt=Mg or Zn).

Abstract: The present invention discloses novel Ruthenium (II) polypyridyl complexes, preparation and its application as DNA imaging agents.

Abstract: The disclosure provides a method of producing a scyllo-inositol or a new scyllo-inositol derivative in a one-step process, from ubiquitous and inexpensive raw materials. Also provided is a scyllo-inositol derivative bonded to saccharides such as glucose and similar.

Abstract: A phosphorylated A2A receptor agonist providing agonist properties on the A2A receptor after dephosphorylation the phosphorylated A2A receptor agonist comprises a ribosyl moiety and a purine moiety and being phosphorylated at the 5?-position of the ribose moiety except adenosine monophosphate (AMP), adenosine diphosphate (ADP) or adenosine triphosphate (ATP), a medicament containing the compound of the invention including ADP and the use of the compound of the invention including ATP and ADP for several medical indications e.g. inflammatory events. In particular, compounds of formula (I) are also disclosed.