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Substituted piperidine amide derivatives and their pharmaceutically acceptable preparation method and in the application of the (by machine translation)

The invention relates to a compound of general formula (I) said substituted piperidine amide derivatives or a stereoisomer thereof, a pharmaceutically acceptable salt, and its preparation method, the drug combination of the local anesthesia or analgesia in and to the use of, the general formula (I) each group definition consistent with the specification; (by machine translation)

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Benzothiazole derivatives with activity as adenosine receptor ligands

The present invention relates to substituted benzothiazole derivitives and to their pharmaceutically acceptable salts useful for the treatment of diseases related to the adenosine receptor.

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PYRROLOPYRIDINE-2-CARBOXYLIC ACID AMIDE INHIBITORS OF GLYCOGEN PHOSHORYLASE

Compounds represented by Formula (I): or pharmaceutically acceptable salts thereof, are inhibitors of glycogen phosphorylase and are useful in the prophylactic or therapeutic treatment of diabetes, hyperglycemia, hypercholesterolemia, hyperinsulinemia, hyperlipidemia, hypertension, atherosclerosis or tissue ischemia e.g. myocardial ischemia, and as cardioprotectants.

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Identification of (R)-N-(4-(4-methoxyphenyl)thiazol-2-yl)-1- tosylpiperidine-2-carboxamide, ML277, as a novel, potent and selective K v7.1 (KCNQ1) potassium channel activator

A high-throughput screen utilizing a depolarization-triggered thallium influx through KCNQ1 channels was developed and used to screen the MLSMR collection of over 300,000 compounds. An iterative medicinal chemistry approach was initiated and from this effort, ML277 was identified as a potent activator of KCNQ1 channels (EC50 = 260 nM). ML277 was shown to be highly selective against other KCNQ channels (>100-fold selectivity versus KCNQ2 and KCNQ4) as well as against the distantly related hERG potassium channel.

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IMIDAZOPYRIDAZINE DERIVATIVES AS RhoIota3Kappabeta INHIBITORS

The present invention relates to substituted imidazopyridazine derivatives of Formula (I) wherein the variables have the meaning defined in the claims. The compounds according to the present invention are useful as pIota3Kappabeta inhibitors. The invention further relates to processes for preparing such novel compounds, pharmaceutical compositions comprising said compounds as an active ingredient as well as the use of said compounds as a medicament.

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Streamlined process for the chemical synthesis of RNA using 2-O-thionocarbamate-protected nucleoside phosphoramidites in the solid phase

An improved method for the chemical synthesis of RNA was developed utilizing a streamlined method for the preparation of phosphoramidite monomers and a single-step deprotection of the resulting oligoribonucleotide product using 1,2-diamines under anhydrous conditions. The process is compatible with most standard heterobase protection and employs a 2?-O-(1,1-dioxo- 1lambda6-thiomorpholine-4-carbothioate) as a unique 2?-hydroxyl protective group. Using this approach, it was demonstrated that the chemical synthesis of RNA can be as simple and robust as the chemical synthesis of DNA.

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Improving the quantum yields of fluorophores by inhibiting twisted intramolecular charge transfer using electron-withdrawing group-functionalized piperidine auxochromes

Herein, we present that the negative inductive effect exerted by electron-withdrawing groups, such as sulfone groups, can obviously improve the ionization potential of amino auxochromes, thereby effectively inhibiting twisted intramolecular charge transfer (TICT) and markedly improving the quantum yields of several families of fluorophores in aqueous solution.

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COMPOSITION COMPRISING TETRACYCLIC COMPOUND

A composition which comprises substance represented by Formula (I), [Meanings of the symbols that are included in the formula are given in the specification as definitions] a pharmaceutically acceptable carrier, and a dissolution aid. is useful for improving solubility, oral absorbability and/or absorbability in blood of a poorly water-soluble or water insoluble tetracyclic compounds having an ALK inhibitory activity that are useful as a prophylactic and/or therapeutic agent for cancer, depression, and cognitive function disorder.

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Chemistry is the science of change. But why do chemical reactions take place? Why do chemicals react with each other? The answer is in thermodynamics and kinetics.In a document type is Article, the author is Gardelli, Cristina and a compound is mentioned, 128453-98-5, 4-(tert-Butoxycarbonyl)thiomorpholine-3-carboxylic acid, introducing its new discovery. 128453-98-5

Discovery and synthesis of HIV integrase inhibitors: Development of potent and orally bioavailable N-methyl pyrimidones

The human immunodeficiency virus type-1 (HIV-1) encodes three enzymes essential for viral replication: a reverse transcriptase, a protease, and an integrase. The latter is responsible for the integration of the viral genome into the human genome and, therefore, represents an attractive target for chemotherapeutic intervention against AIDS. A drug based on this mechanism has not yet been approved. Benzyl-dihydroxypyrimidine-carboxamides were discovered in our laboratories as a novel and metabolically stable class of agents that exhibits potent inhibition of the HIV integrase strand transfer step. Further efforts led to very potent compounds based on the structurally related N-Me pyrimidone scaffold. One of the more interesting compounds in this series is the 2-N-Me-morpholino derivative 27a, which shows a CIC95 of 65 nM in the cell in the presence of serum. The compound has favorable pharmacokinetic properties in three preclinical species and shows no liabilities in several counterscreening assays.

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Second generation 2-pyridyl biphenyl amide inhibitors of the hedgehog pathway

Potent and efficacious inhibitors of the hedgehog pathway for the treatment of cancer have been prepared using the 2-pyridyl biphenyl amide scaffold common to the clinical lead GDC-0449. Analogs with polar groups in the para-position of the aryl amide ring optimized potency, had minimal CYP inhibition, and possessed good exposure in rats. Compounds 9d and 14f potently inhibited hedgehog signaling as measured by Gli1 mRNA and were found to be equivalent or more potent than GDC-0449, respectively, when studied in a Ptch+/- medulloblastoma allograft model, that is, highly dependent on hedgehog signaling.

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