Abstract: The present invention relates to oligooxopiperazines for reactivating p53. The oligooxopiperazines comprise two or three oxopiperazine rings and substantially mimic helix ?B of the C-terminal transactivation domain of Hypoxia-Inducible Factor 1?. Methods of using the oligooxopiperazines are also disclosed. Exemplary oligooxopiperazines include those of Formula I below (wherein A, R1, R2, R3, R4, and B are as defined herein).

Abstract: Disclosed are compounds of formula (I); or a pharmaceutically acceptable salt thereof; wherein Y, Ra, Ra?, Rc, Rf, X2, Rd, Rd?, Re, Re?, m, and G have the values described herein and stereochemical configurations depicted at asterisked positions indicate absolute stereochemistry, useful as inhibitors of Sumo Activating Enzyme (SAE). Further provided are pharmaceutical compositions comprising a compound of the disclosure and methods of using the compositions in the treatment of proliferative, inflammatory, cardiovascular and neurodegenerative diseases or disorders.

Abstract: Disclosed are compounds of Formula 1, including all stereoisomers, N-oxides, and salts thereof, wherein each Y1, Y2, Y3, Y4, Z, R2, m and R3 are as defined in the disclosure. Also disclosed are compositions containing a compound of Formula 1 and methods for controlling undesired vegetation comprising contacting the undesired vegetation or its environment with an effective amount of a compound or a composition of the invention.

Abstract: Provided herein are compounds of Formula (I) or (II): (I) (II) pharmaceutically acceptable salts, tautomers, prodrugs, and stereoisomers thereof, and pharmaceutical compositions thereof, wherein X, RN, R1, R3, R4, p, and m are as defined herein. Such compounds and compositions have been found useful in the treatment or prevention of viral infections, e.g., polyomaviral infections, and are further envisioned useful in treatment or prevention of other pathogenic conditions associated with endosomal trafficking. Methods of treating or preventing an infection by a pathogen secreting an AB5 toxin is also contemplated.

Abstract: Methods for improving mitochondrial function, decreasing iron accumulation, and/or decreasing oxidative stress by exposing cells or treating a subject to compounds or compositions of the general formula are described that are beneficial in treating, for example, diseases and conditions such as Friedreich's ataxia, normal aging, and various neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. Furthermore, such compounds are useful as probes for identifying defects in mitochondrial metabolism, mitochondrial iron accumulation, cellular stress among other mitochondrial diseases and helping to identify compounds active in overcoming such defects.

Abstract: A composition comprising a dibenzo[f,h]quinoxaline derivative in which impurities are reduced and a method of synthesizing dibenzo[f,h]quinoxaline in which impurities are reduced are provided. In addition, a light-emitting element, a light-emitting device, an electronic appliance, or a lighting device with high emission efficiency and high reliability in which dibenzo[f,h]quinoxaline is used as an EL material is provided. In the synthesis method, 2-(chloroaryl)dibenzo[f,h]quinoxaline is used as a synthetic intermediate in a synthetic pathway so that an impurity contained in a final product can be removed easily by purification by sublimation.

Abstract: The present invention relates to a process for the preparation of canagliflozin and intermediates thereof.

Abstract: Anti-angiogenic treatments, treatments of hyperpermeability disorders, treatments of neuropathic and neurodegenerative disorders, pain treatments, methods of reducing the risk of pre-eclampsia and compounds for use in such methods are described.

Abstract: Disclosed are compounds having the formula: wherein X is as defined herein, and methods of making and using the same.

Abstract: The present invention includes compounds having structural formula (Ia): or salts or solvates thereof. These compounds are useful as sweet flavor modifiers. The present invention also includes compositions comprising the present compounds and methods of enhancing the sweet taste of compositions.

Abstract: The present invention is directed to thiazole compounds which are antagonists of orexin receptors. The present invention is also directed to uses of the thiazole compounds described herein in the potential treatment or prevention of neurological and psychiatric disorders and diseases in which orexin receptors are involved. The present invention is also directed to pharmaceutical compositions comprising these compounds. The present invention is also directed to uses of these pharmaceutical compositions in the prevention or treatment of such diseases in which orexin receptors are involved.

Abstract: The present invention relates to crystalline forms of pyrroloquinoline quinone disodium salt. The present invention provides crystalline Form A and crystalline Form B of pyrroloquinoline quinone disodium salt, and the methods and uses for the preparation thereof. The X-ray powder diffraction patterns of crystalline Form A and crystalline Form B are as shown by FIG. 1 and FIG. 5, respectively. The crystalline forms of the present invention have low moisture absorption and high stability, as well as excellent use and storage performances.

Abstract: Described herein are inhibitors of FGFR-4, pharmaceutical compositions including such compounds, and methods of using such compounds and compositions to inhibit the activity of FGFR-4.

Abstract: In one aspect this invention relates generally to compounds of Formula: and sub-formulas thereof, or a tautomer of each thereof, a pharmaceutically acceptable salt of each thereof, or a pharmaceutically acceptable solvate of each of the foregoing, where X1, L1, L3, and R3 are described herein.

Abstract: The present invention is directed to [1,2,4]triazolo[1,5-a]pyridine and [1,2,4]triazolo[1,5-a]pyrazine derivatives of Formula I, or a pharmaceutically acceptable salt thereof, which are LSD1 inhibitors useful in the treatment of diseases such as cancer.

Abstract: The present invention is directed to imidazo[1,5-a]pyridine and imidazo[1,5-a]pyrazine derivatives of Formula I, or a pharmaceutically acceptable salt thereof, which are LSD1 inhibitors useful in the treatment of diseases such as cancer.

Abstract: Provided herein are intermediates and processes useful for facile synthesis of biologically active molecules.

Abstract: The present disclosure relates to novel compounds, methods, and compositions capable of inhibiting HIF hydroxylase enzyme activity, thereby increasing the stability and/or activity of hypoxia inducible factor (HIF).

Abstract: The present invention provides novel 3,4-disubstituted-1H-pyrrolo[2,3-b]pyridine derivatives and 4,5-disubstituted-7H-pyrrolo[2,3-c]pyridazine derivatives of Formula I, and the pharmaceutically acceptable salts thereof wherein R1, R2, R3, R4 and X are as defined in the specification. The invention is also directed to pharmaceutical compositions comprising the compounds of formula I and to use of the compounds in the treatment of diseases associated with LRRK2, such as neurodegenerative diseases including Parkinson's disease or Alzheimer's disease, cancer, Crohn's disease or leprosy.

Abstract: The present invention provides compounds of any one of Formulae (I), (II-C) (e.g., Formula (II)), and (III), and pharmaceutically compositions thereof. Compounds of any one of Formulae (I), (II-C), and (III) are believed to be binders of bromodomains and/or bromodomain-containing proteins (e.g., bromo and extra terminal (BET) proteins). Also provided are methods, uses, and kits using the compounds and pharmaceutical compositions for inhibiting the activity (e.g., increased activity) of bromodomains and/or bromodomain-containing proteins and for treating and/or preventing in a subject diseases associated with bromodomains or bromodomain-containing proteins (e.g., proliferative diseases, cardiovascular diseases, viral infections, fibrotic diseases, metabolic diseases, endocrine diseases, and radiation poisoning). The compounds, pharmaceutical compositions, and kits are also useful for male contraception.

Abstract: The present invention relates to the use of ergot derivatives or ergolines, and in particular of lisuride and terguride for the prophylaxis and treatment of constrictive capillary arteriopathy. Constrictive capillary arteriopathy refers to the diseases pulmonary arterial hypertension, endogenously induced or exogenously induced glomerulosclerosis as well as secondary Raynaud's syndrome.

Abstract: Disclosed are compounds that inhibit breast cancer resistance protein (BCRP), of which compound (I-1), ((3S,6S,12aS)-6-isobutyl-9-methoxy-3-methyl-2,3,6,7,12,12a-hexahydropyrazino[1?,2?:1,6]pyrido[3,4-b]indole-1,4-dione) or a pharmaceutically acceptable salt thereof, and the compound 12, ((3S,6S,12aS)-6-isobutyl-9-methoxy-3,10-dimethyl-2,3,6,7,12,12a-hexahydropyrazino[1?,2?:1,6]pyrido[3,4-b]indole-1,4-dione) or a pharmaceutically acceptable salt thereof. Also disclosed are methods of inhibiting BCRP or decreasing BCRP activity and methods of determining potential BCRP substrates.

Abstract: Disclosed are novel nitrogen-containing, heterocyclic, c-Met inhibitor compounds, processes for their preparation and formulations thereof. The compounds are useful as therapeutical agents for the inhibition, regulation, and control of c-Met kinase signal pathway, and useful for treating in a subject a cell proliferative disorder or disorders mediated by c-Met.

Abstract: The disclosure generally relates to the novel compounds of formula I, including pharmaceutically acceptable salts, which are CGRP receptor antagonists. The disclosure also relates to pharmaceutical compositions and methods for using the compounds in the treatment of CGRP related disorders including migraine and other headaches, neurogenic vasodilation, neurogenic inflammation, thermal injury, circulatory shock, flushing associated with menopause, airway inflammatory diseases such as asthma, and chronic obstructive pulmonary disease (COPD).

Abstract: An improved method of preparing tetranitroglycoluril (TNGU) via the in situ decomposition of a nitrimino group with elimination of nitrogen without the use of dinitrogen pentoxide. The compound is useful as a high energy, high density explosive or propellant oxidizer.

Abstract: The hedgehog (Hh) signaling pathway is a pathway which regulates patterning, growth and cell migration during embryonic development, but in adulthood is limited to tissue maintenance and repair. Mutational inactivation of the inhibitory pathway components leads to constitutive ligand-independent activation of the Hh signaling pathway, results in cancers such as basal cell carcinoma and medulloblastoma. Ligand-dependent activation of Hh signaling is involved in prostate cancer, pancreatic cancer, breast cancer and some blood cancers. Therefore, inhibition of the aberrant Hh signaling represents a promising approach toward novel anticancer therapy. The present invention provides novel molecules of formula I that inhibit hedgehog pathway signaling and provides therapeutic applications for the treatment of malignancies (basal cell carcinoma, medulloblastoma, glioblastoma, non-small cell lung cancer, prostate cancer, pancreatic cancer, blood cancers, mesenchymal cancers, etc.

Abstract: The present invention relates to compounds that bind to and otherwise modulate the activity of bromodomain-containing proteins, to processes for preparing these compounds, to pharmaceutical compositions containing these compounds, and to methods of using these compounds for treating a wide variety of conditions and disorders.

Abstract: The present invention is directed to imidazo[1,2-a]pyrazine derivatives of Formula I, or a pharmaceutically acceptable salt thereof, which are LSD1 inhibitors useful in the treatment of diseases such as cancer.

Abstract: The present invention relates to a kind of new hydroximic acid derivatives, in particular, hydroximic acid derivatives of pyrazolopyrimidine and their medical applications, which have inhibition to histone deacetylase 1 and two kinds of tyrosine kinases (vascular endothelial cell growth factor receptors as well as platelet-derived growth factor receptors) simultaneously, and thus can be used for treatment of diseases related to those three kinds of enzymes. This kind of compounds both exerts a synergistic effect sufficiently to increase biological activity, and avoids problems caused by different properties and metabolisms, therefore is more practical and has good prospects.

Abstract: Compounds of formula I, in which LA, LB, LC, ring A, ring B, RA, RB, RC, RD, RE and RF are defined in the description, and which are protein kinases inhibitors. The invention also relates to pharmaceutical compositions containing said compounds and also to the use of those compounds for treatment and/or prevention of diseases related with aberrant protein kinase activity.

Abstract: The present invention is directed to compounds of Formula I: wherein A is phenyl, naphthalenyl, pyridyl, quinolinyl, isoquinolinyl, imidazopyridyl, furanyl, thiazolyl, isoxazolyl, pyrazolyl, imidazothiazolyl, benzimidazolyl, or indazolyl; R1 is H, alkyl, alkoxy, hydroxyalkylene, OH, halo, phenyl, triazolyl, oxazolyl, isoxazolyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, piperazinyl, pyrazolyl, oxadiazolyl, pyrrolidinyl, thiophenyl, morpholinyl, or dialkylamino; R2 is H, alkyl, alkoxy, hydroxyalkylene, or halo; Z is NH, N-alkyl, or O; R5 is pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, quinazolinyl, quinoxalinyl, pyrazolyl, benzoxazolyl, imidazopyrazinyl, or triazolopyrazinyl, optionally substituted with a one or two substituents independently selected from the group consisting of alkyl, alkoxy, or halo; and n is 0 or 1. Methods of making the compounds of Formula I are also described. The invention also relates to pharmaceutical compositions comprising compounds of Formula I.

Abstract: Described herein are compounds of Formula (I) pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Methods of using the compounds or pharmaceutical compositions thereof for treating diseases are also provided.

Abstract: This invention is directed to methods of preparing certain spiro-oxindole derivatives, which are useful for the treatment and/or prevention of sodium channel-mediated diseases or conditions, such as pain.

Abstract: An alicyclic diepoxy compound represented by the following general formula (1): (in the general formula (1), R1 and R2 each independently represent one selected from the group consisting of a hydrogen atom, alkyl groups having 1 to 10 carbon atoms, and a fluorine atom, and n represents an integer of 2 to 5).

Abstract: Disclosed is a compound of formula 1, or a pharmaceutically acceptable salt thereof, where R1, R2, R3, R4, R5, R6, R7, R7?, R8, R9, R10, R11, R12 and R13 are as disclosed herein. Also, disclosed is a process for the preparation of the compound of formula 1, or a pharmaceutically acceptable salt thereof, and intermediates used therein. The compound of formula 1 can be used in the preparation of halichondrin analogs, such as Eribulin; and a process for its preparation from the compound of formula 1 is also disclosed.

Abstract: In general, the present invention features improved methods useful for the synthesis of analogs of halichondrin B, such as eribulin and pharmaceutically acceptable salts thereof (e.g., eribulin mesylate).

Abstract: Cleavable crosslinkers of Formula (I) useful reagents in biochemical drug research and development such as antibody drug conjugates are disclosed.

Abstract: The invention relates to novel conjugated polymers containing one or more thieno[3,2-b]thiophene based polycyclic repeating units, to methods for their preparation and educts or intermediates used therein, to polymer blends, mixtures and formulations containing them, to the use of the polymers, polymer blends, mixtures and formulations as organic semiconductors in organic electronic (OE) devices, especially in organic photovoltaic (OPV) devices and organic photodetectors (OPD), and to OE, OPV and OPD devices comprising these polymers, polymer blends, mixtures or formulations.

Abstract: Conformationally restricted, spatially defined 12-30 membered macrocyclic ring systems of type (I) are constituted by three distinct building blocks: an aromatic template a, a conformation modulator b and a spacer moiety c as detailed in the description and the claims. Macrocycles of type (I) are readily manufactured by parallel synthesis or combinatorial chemistry. They are designed to interact with specific biological targets. In particular, they show agonistic or antagonistic activity on the motilin receptor (MR receptor), on the serotonin receptor of subtype 5-HT2B (5-HT2B receptor), and on the prostaglandin F2•receptor (FP receptor). They are thus potentially useful for the treatment of hypomotility disorders of the gastrointestinal tract such as diabetic gastroparesis and constipation type irritable bowl syndrome; of CNS related diseases like migraine, schizophrenia, psychosis or depression; of ocular hypertension such as associated with glaucoma and preterm labour.

Abstract: The present disclosure relates to compounds that are sodium channel inhibitors and to their use in the treatment of various disease states, including cardiovascular diseases and diabetes. In particular embodiments, the structure of the compounds is given by Formula I: wherein Y, Z, n, R1 and R3 are as described herein, to methods for the preparation and use of the compounds and to pharmaceutical compositions containing the same.

Abstract: Inhibitors of Plasmodium falciparum equilibrative nucleoside transporter type 1 are identified and methods of use as anti-parasitic compounds are provided.

Abstract: The present invention relates to methods and compositions for inhibiting the activity of skin proteases, especially human kallikrein 7 (KLK7), human kallikrein 5 (KLK5), and human kallikrein 14 (KLK14). More specifically, the invention relates to the use of substituted 3,1-benzoxazin-4-ones being selective inhibitors of human skin kallikreins for the treatment of skin diseases, more specifically for the treatment of inflammatory skins diseases, especially Netherton syndrome.

Abstract: The present invention provides compounds of the formula: that are 5HT3 receptor antagonists and are therefore useful for the treatment of diseases treatable by inhibition of 5HT3 receptor such as emesis, pain, drug addiction, neurodegenerative and psychiatric disorders, and GI disorders. Also provided are pharmaceutical compositions containing such compounds and processes for preparing such compounds.

Abstract: This disclosure relates to an improved synthesis of cephalosporin antibiotic compounds such as ceftolozane, and compositions and methods of use thereof. Thiadiazolyl-oximinoacetic acid compounds such as TATD can be reacted to yield the activated thiadiazolyl-oximinoacetic acid methanesulfonate ester compounds useful in the manufacture of cephalosporin antibiotic compounds.

Abstract: The invention provides compounds with enhanced permeability for selectively inhibiting glycosidases, prodrugs of the compounds, and pharmaceutical compositions including the compounds or prodrugs of the compounds. The invention also provides methods of treating diseases and disorders related to deficiency or overexpression of O-GlcNAcase, accumulation or deficiency of O-GlcNAc.

Abstract: The present invention provides a compound of Formula (I) where A is a heterocycle ring system and B is a heterocycle ring system or aryl ring system, and pharmaceutical compositions comprising one or more said compounds, and methods for using said compounds for treating or preventing thromboses, embolisms, hypercoagulability or fibrotic changes.

Abstract: The present invention discloses pyridoinolobenzo[b,e]diazepine and thiazepine derivatives of Formula 1, wherein X is NR10, S, S(O), or S(O)2. Y is a single bond or no bond. A and B are independently (CH2)m and (CH2)n respectively; and the subscripts ‘m’ and ‘n’ independently vary from 1 to 4. R1 to R9 are various electron donating, electron withdrawing, hydrophilic, or lipophilic groups selected to optimize the physicochemical and biological properties of compounds of Formula I.

Abstract: Disclosed herein are heterocyclic compounds and compositions useful in the treatment of ITK mediated diseases, such as inflammation, having the structure of Formula (I): wherein R1, R2, and X are as defined in the detailed description. Methods of inhibition of ITK activity in a human or animal subject are also provided.

Abstract: The invention relates to a process for preparing trialkylmetal compounds of the general formula R3M (where M=metal of group IIIA of the Periodic Table of the Elements (PTE), preferably gallium or indium, and R=C1-C5-alkyl, preferably methyl or ethyl). The process is based on the reaction of metal trichloride (MeCl3) with alkylaluminium sesquichloride (R3Al2Cl3) in the presence of at least one alkali metal halide as auxiliary base. The reaction mixture is heated to a temperature above 120° C. and the trialkylmetal compound is separated off from the reaction mixture via a separator, with partially alkylated products being at the same time recirculated to the reaction mixture. In a further step, the reaction mixture is heated to a maximum of 350° C. and the remaining alkylated and partially alkylated products are separated off. The products obtained in this way can optionally be recycled in the process.

Abstract: The invention relates to a method for producing siloxanes selectively carrying primary amino groups by reacting them with ammonia, and to compounds produced in this way.