Archives for Chemistry Experiments of Methyl 4-bromobenzo[b]thiophene-2-carboxylate

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The present invention relates to compounds of formula (I) or pharmaceutical acceptable salts, wherein A, R1, R2, R3 and m, are defined in the description. The present invention relates also to methods of making said compounds, and compositions containing said compounds which are useful for inhibiting kinases such as Glycogen Synthase kinase 3 (GSK-3), Rho kinase (ROCK), Janus Kinases (JAK), AKT, PAK4, PLK, CK2, KDR, MK2, JNK1, aurora, pim 1 and nek 2.

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COMPOUNDS ACTING AT MULTIPLE PROSTAGLANDIN RECEPTORS GIVING A GENERAL ANTI-INFLAMMATORY RESPONSE

The present invention provides a compound, that is a 1-({halo-2-[(2-hydrocarbyl or substituted hydrocarbyl)oxy]phenyl}methyl)-(fused bicyclic nitrogen heteroaryl) carboxylic acid or an ester or sulfonamide thereof. The compound may be represented by the following formula I, Wherein R1, R2, R3, R4 A, X, W, Z and Y are as defined in the specification. The compounds may be administered to treat DP, FP, EP1, TP and/or EP4 receptor-mediated diseases or conditions.

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Extracurricular laboratory:new discovery of Methyl 4-bromobenzo[b]thiophene-2-carboxylate

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360575-29-7, Name is Methyl 4-bromobenzo[b]thiophene-2-carboxylate, belongs to benzothiophene compound, is a common compound. Formula: C10H7BrO2SIn an article, once mentioned the new application about 360575-29-7.

Hysteretic carbon dioxide sorption in a novel copper(ii)-indazole- carboxylate porous coordination polymer

The synthesis, structural and gas sorption studies of a porous Cu(ii) coordination polymer featuring 1H-indazole-5-carboxylic acid (H2L) are presented. [Cu(HL)2] is a thermally and hydrolytically robust 4-connected 3D coordination polymer of NbO topology and is replete with 1D channels that permit selective and hysteretic sorption of CO2. The Royal Society of Chemistry 2012.

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Convergent and enantioselective syntheses of cytosolic phospholipase A 2alpha inhibiting N-(1-indazol-1-ylpropan-2-yl)carbamates

Cytosolic phospholipase A2alpha (cPLA2alpha) is an important enzyme of the inflammation cascade. Therefore, inhibitors of cPLA2alpha are assumed to be promising drug candidates for the treatment of inflammatory disorders. Recently we have found that indole-5-carboxylic acid with a 3-(4-octylphenoxy)-2-(phenoxycarbonylamino) propyl substituent in position 1 is an inhibitor of cPLA2alpha. We have now synthesized a corresponding derivative with the indole heterocycle replaced by an indazole (4) employing an analogous reaction sequence as for the synthesis of the indole derivative. Besides, a more convergent synthesis for 4 was established using an aziridine as central intermediate. Furthermore, a chiral-pool based enantioselective synthesis was developed for the synthesis of (R)- and (S)-4. Starting compound for both enantiomers was the (R)-serine derived oxazolidine (R)-25. Compound 4 proved to be a moderate inhibitor of cPLA2alpha, with the S-enantiomer being twice as active as the R-enantiomer. The racemate 4 and the enantiomers (R)- and (S)-4 showed a high in vitro metabolic stability in rat liver S9 fractions. This journal is the Partner Organisations 2014.

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Carboxamides vs. methanimines: Crystal structures, binding interactions, photophysical studies, and biological evaluation of (indazole-5-yl)methanimines as monoamine oxidase B and acetylcholinesterase inhibitors

A comprehensive study was performed for the first time to compare two structurally related substance classes, namely indazole-5-carboxamides (11?16) and (indazole-5-yl)methanimines (17?22). Both chemical entities are potent, selective and reversible MAO-B inhibitors and, therefore, may serve as promising lead structures for the development of drug candidates against Parkinson’s disease (PD) and other neurological disorders. Compounds 15 (Ki = 170 pM, SI = 25907) and 17 (Ki = 270 pM, SI = 16340) were the most potent and selective MAO-B inhibitors in both series. To investigate the multi-target inhibitory activity, all compounds were further screened for their potency against human AChE and BuChE enzymes. Compound 15 was found to be the most potent and selective AChE inhibitor in all series (hAChE IC50 = 78.3 ± 1.7 muM). Moreover, compounds 11 and 17 showed no risk of drug-induced hepatotoxicity and a wider safety window, as determined in preliminary cytotoxicity screening. Molecular modeling studies into the human MAO-B enzyme-binding site supported by a HYDE analysis suggested that the imine linker similarly contributes to the total binding energy in methanimines 17?22 as the amide spacer in their carboxamide analogs 11?16. Amplified photophysical evaluation of compounds 17 and 20, including single X-ray analysis, photochemical experiments, and quantum-chemical calculations, provided insights into their more favourable isomeric forms and structural features, which contribute to their biologically active form and promising drug-like properties.

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Identification of N-acylhydrazone derivatives as novel lactate dehydrogenase A inhibitors

Abstract Glycolysis is drastically increased in tumors and it is the main route to energy production with a minor use of oxidative phosphorylation. Among the key enzymes in the glycolytic process, LDH is emerging as one of the most interesting targets for the development of new inhibitors. In this context, in the present work, we carried out a virtual screening procedure followed by chemical modifications of the identified structures according to a “hit-to-lead” process. The effects of the new molecules were preliminary probed against purified human LDH-A. The compounds active at low micromolar level were additionally characterized for their activity on some cellular metabolic processes by using Raji human cell line. Within the series, 1 was considered the best candidate, and a more detailed characterization of its biological properties was performed. In Raji cells exposed to compound 1 we evidenced the occurrence of effects usually observed in cancer cells after LDH-A inhibition: reduced lactate production and NAD/NADH ratio, apoptosis. The flow cytometry analysis of treated cells also showed cell cycle changes compatible with effects exerted at the glycolytic level. Finally, in agreement with the data obtained with other inhibitors or by silencing LDH-A expression, compound 1 was found to increase Raji cells response to some commonly used chemotherapeutic agents. Taken together, all these finding are in support of the LDH-A inhibiting activity of compound 1.

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Benzothiophene – Wikipedia,
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Enzyme inhibitors cause a decrease in the reaction rate of an enzyme-catalyzed reaction by binding to a specific portion of an enzyme and thus slowing or preventing a reaction from occurring.SDS of cas: 360575-29-7, such as the rate of change in the concentration of reactants or products with time.In a article, mentioned the application of 360575-29-7, Name is Methyl 4-bromobenzo[b]thiophene-2-carboxylate, molecular formula is C10H7BrO2S

A method for inhibiting ROCK compound and its application (by machine translation)

The present invention discloses a compound of the formula I as shown, or a stereoisomer thereof, or a pharmaceutically acceptable salt, or solvate thereof, or prodrug thereof, or its metabolic product. The test shows, the compounds of the invention has good ROCK inhibition activity, can be effectively used for ROCK activity with abnormal in the treatment of diseases, for the clinical treatment of diseases associated with abnormal active ROCK provides a new pharmaceutical may be. (by machine translation)

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Benzothiophene – Wikipedia,
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Off-DNA DNA-Encoded Library Affinity Screening

DNA-encoded library (DEL) technology is emerging as a key element of the small molecule discovery toolbox. Conventional DEL screens (i.e., on-DNA screening) interrogate large combinatorial libraries via affinity selection of DNA-tagged library members that are ligands of a purified and immobilized protein target. In these selections, the DNA tags can materially and undesirably influence target binding and, therefore, the experiment outcome. Here, we use a solid-phase DEL and droplet-based microfluidic screening to separate the DEL member from its DNA tag (i.e., off-DNA screening), for subsequent in-droplet laser-induced fluorescence polarization (FP) detection of target binding, obviating DNA tag interference. Using the receptor tyrosine kinase (RTK) discoidin domain receptor 1 (DDR1) as a proof-of-concept target in a droplet-scale competition-binding assay, we screened a 67 100-member solid-phase DEL of drug-like small molecules for competitive ligands of DDR1 and identified several known RTK inhibitor pharmacophores, including azaindole- and quinazolinone-containing monomers. Off-DNA DEL affinity screening with FP detection is potentially amenable to a wide array of target classes, including nucleic acid binding proteins, proteins that are difficult to overexpress and purify, or targets with no known activity assay.

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THIAZOLOPYRIMIDINE COMPOUNDS

The present invention relates to the use of novel pyrrolopyrazine derivatives of formula I: wherein all variable substituents are defined as described herein, which are SYK inhibitors and are useful for the treatment of auto-immune and inflammatory diseases.

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HETEROCYCLIC COMPOUNDS FOR THE INHIBITION OF PASK

Disclosed herein are new heterocyclic compounds and compositions and their application as pharmaceuticals for the treatment of disease. Methods of inhibiting PAS Kinase (PASK) activity in a human or animal subject are also provided for the treatment of diseases such as diabetes mellitus.

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Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem