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Identification of the structural requirements of the receptor-binding affinity of diphenolic azoles to estrogen receptors alpha and beta by three-dimensional quantitative structure-activity relationship and structure-activity relationship analysis

Three-dimensional (31)) quantitative structure-activity relationship (QSAR) and structure-activity relationship (SAR) analyses were applied concurrently to a data set of highly selective estrogen receptor beta (ER beta) agonists. The data set consisted of diphenolic azoles characterized by similar structural skeletons but with different binding modes to the estrogen receptor site. Models were developed separately with respect to the relative binding affinities (RBAs) to ER alpha and ER beta. Steric and electrostatic fields were calculated for a training set of 72 compounds using comparative molecular field analysis (CoMFA). The model developed for ER alpha RBA yielded R-2 of 0.91 and q(cv)(2) of 0.60. The model developed for ER beta RBA yielded R-2 of 0.95 and q(cv)(2) of 0.40. Both models were validated successfully using an external test set of 32 compounds. A new concept of test set evaluation based on the variability of the biological response due to the variability of the living organism has been introduced. The CoMFA analysis was supported by a SAR study. In addition to the most favorable steric and electrostatic regions identified by CoMFA, a number of structural descriptors were identified as being important for binding. These are the number of substituents attached to the main skeleton of each compound, the largest distance between the oxygen atoms of each molecule, and the angle defined by the planes that split the phenyl or the naphthyl and the benzisoxazole or the benzoxazole moiety in a morphometrically longitudinal way.

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Reference:
Benzisoxazole – Wikipedia,
,Benzisoxazole – an overview | ScienceDirect Topics

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The proportionality constant is the rate constant for the particular unimolecular reaction. the reaction rate is directly proportional to the concentration of the reactant. I hope my blog about 298-12-4 is helpful to your research. Product Details of 298-12-4.

Catalysts are substances that increase the reaction rate of a chemical reaction without being consumed in the process. 298-12-4, Name is 2-Oxoacetic acid, SMILES is OC(=O)C=O, belongs to Benzisoxazole compound. In a document, author is Jadhav, VK, introduce the new discover, Product Details of 298-12-4.

Sodium perborate: A facile synthesis of 1,2-benzisoxazole 2-oxides

An efficient and convenient methodology has been developed for the conversion of 2-hydroxy phenyl ketoxime to 1,2-benzisoxazole 2-oxide with sodium perborate (SPB) in glacial acetic acid under mild reaction conditions. Interestingly when the reaction was carried out under reflux condition deoximation was observed in quantitative yield.

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Reference:
Benzisoxazole – Wikipedia,
,Benzisoxazole – an overview | ScienceDirect Topics

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In an article, author is Srivastava, S, once mentioned the application of 298-12-4, Computed Properties of C2H2O3, Name is 2-Oxoacetic acid, molecular formula is C2H2O3, molecular weight is 74.0355, MDL number is MFCD00006958, category is Benzisoxazole. Now introduce a scientific discovery about this category.

Photolysis of 3-hydroxy-2,3-dihydro-2,1-benzisoxazole derivatives studied by EPR spectroscopy: Competing N-O and C-O bond scission

Photolysis of 3-hydroxy-2,3-dihydro-2,1-benzisoxazole derivatives gives 2-acetylaniline derivatives as the sole stable products. EPR spectroscopy shows that persistent arylnitroxyl radicals are formed as intermediates and then further photolyzed. A mechanism accounting for these observations is proposed. (C) 1996 Elsevier Science Ltd

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Reference:
Benzisoxazole – Wikipedia,
,Benzisoxazole – an overview | ScienceDirect Topics

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Selective inhibitors of glial GABA uptake: Synthesis, absolute stereochemistry, and pharmacology of the enantiomers of 3-hydroxy-4-amino-4,5,6,7-tetrahydro-1,2-benzisoxazole (exo-THPO) and analogues

3-Methoxy-4,5,6,7-tetrahydro-1,2-benzisoxazol-4-one (20a), or the corresponding 3-ethoxy analogue (20b), and 3-chloro-4,5,6,7-tetrahydro-1,2-benzisothiazol-4-one (51) were synthesized by regioselective chromic acid oxidation of the respective bicyclic tetrahydrobenzenes 19a,b and 50, and they were used as key intermediates for the syntheses of the target; zwitterionic 3-isoxazolols 8-15 and 3-isothiazolols 16 and 17, respectively. These reaction sequences involved different reductive processes. Whereas (RS)-4-amino-3-hydroxy-4,5,6,7-tetrahydro-1,2-benzisoxazole (8, exo-THPO) was synthesized via aluminum amalgam reduction of oxime 22a or 22b, compounds 9,11-13, and 15-17 were obtained via reductive aminations. Compound 10 was synthesized via N-ethylation of the N-Boc-protected primary amine 25. The enantiomers of 8 were obtained in high enantiomeric purities (ee greater than or equal to 99.1%) via the diastereomeric amides 32 and 33, synthesized from the primary amine 23b and (R)-alpha-methoxyphenylacetyl chloride and subsequent separation by preparative HPLC. The enantiomers of 9 were prepared analogously from the secondary amine 27. On the basis of X-ray crystallographic analyses, the configuration of oxime 22a was shown to be E and the absolute configurations of (-)-8 . HCl and (+)-9 . HBr were established to be R. The effects of the target compounds on GABA uptake mechanisms in vitro were measured using a rat brain synaptosomal preparation and primary cultures of mouse cortical neurons and glia cells (astrocytes). Whereas the classical GABA uptake inhibitor, (R)-nipecotic acid (2), nonselectively inhibits neuronal (IC50 = 12 mu M) and glial (IC50 = 16 mu M) GABA uptake and 4,5,6,7-tetrahydroisoxazolo[4,5-c]pyridin-3-ol (1, THPO) shows some selectivity for glial (IC50 = 268 mu M) versus neuronal (IC50 = 530 mu M) GABA uptake, exo-THPO (8) was shown to be more potent as an inhibitor of glial (IC50 = 200 mu M) rather than neuronal (IC50 = 900 mu M) GABA uptake. This selectivity was more pronounced for 9, which showed IC50 values of 40 and 500 mu M as an inhibitor of glial and neuronal GABA uptake, respectively. These effects of 8 and 9 proved to be enantioselective, (R)-(-)-8 and (R)-(+)-9 being the active inhibitors of both uptake systems. The selectivity of 9 as a glial GABA uptake inhibitor was largely lost by replacing the N-methyl group of 9 by an ethyl group, compound 10 being an almost equipotent inhibitor of glial (IC50 = 280 mu M) and neuronal (IC50 = 400 mu M) GABA uptake. The remaining target compounds, 11-17, were very weak or inactive as inhibitors of both uptake systems. Compounds 9-13 and 15 were shown to be essentially inactive against isoniazide-induced convulsions in mice after subcutaneous administration. The isomeric pivaloyloxymethyl derivatives of 9, compounds 43 and 44, were synthesized and tested as potential prodrugs in the isoniazide animal model. Both 43 (ED50 = 150 mu mol/kg) and 44 (ED50 = 220 mu mol/kg) showed anticonvulsant effects, and this effect of 43 was shown to reside in the (R)-(+)-enantiomer, 45 (ED50 = 44 mu mol/kg). Compound 9 also showed anticonvulsant activity when administered intracerebroventricularly (ED50 = 59 nmol).

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Reference:
Benzisoxazole – Wikipedia,
,Benzisoxazole – an overview | ScienceDirect Topics

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The proportionality constant is the rate constant for the particular unimolecular reaction. the reaction rate is directly proportional to the concentration of the reactant. I hope my blog about 298-12-4 is helpful to your research. COA of Formula: C2H2O3.

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, 298-12-4, Name is 2-Oxoacetic acid, SMILES is OC(=O)C=O, belongs to Benzisoxazole compound. In a document, author is Shastri, RA, introduce the new discover, COA of Formula: C2H2O3.

Mass spectra of some 3-beta-bromoethyl-1,2-benzisoxazoles

Fragmentation pattern of some 3-β-bromothyl-1,2-benzisoxazole is studied.

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Reference:
Benzisoxazole – Wikipedia,
,Benzisoxazole – an overview | ScienceDirect Topics

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Reference of 298-12-4, As an important bridge between the micro and macro material world, chemistry is one of the main methods and means for humans to understand and transform the material world. 298-12-4, Name is 2-Oxoacetic acid, SMILES is OC(=O)C=O, belongs to Benzisoxazole compound. In a article, author is Murata, M., introduce new discover of the category.

ZONISAMIDE: A NEW DRUG FOR PARKINSON’S DISEASE

Zonisamide, a benzisoxazole derivative, is an antiepileptic drug with a long half-life. Three nationwide, double-blind, placebo-controlled studies carried out in Japan prompted the approval of zonisamide as an antiparkinsonian agent in early 2009. The addition of zonisamide at 25-50 mg/day to currently used antiparkinsonian drugs significantly improved cardinal symptoms in patients with advanced Parkinson’s disease. The effects were maintained over more than 1 year even in patients with advanced disease. Zonisamide has multiple modes of action, and its effects on Parkinson’s disease include activation of dopamine synthesis, inhibition of monoamine oxidase, inhibition of T-type calcium channels and inhibition of an indirect pathway in the basal ganglia through the delta opioid receptor Furthermore, zonisamide exhibits neuroprotective effects in animal models of Parkinson’s disease. It strongly inhibits quinoprotein formation and markedly increases glutathione S-transferase levels in the striatum by enhancing the astroglial cysteine transport system and/or astroglial proliferation via S100 beta production and secretion.

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Reference:
Benzisoxazole – Wikipedia,
,Benzisoxazole – an overview | ScienceDirect Topics

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Benzisoxazole: a privileged scaffold for medicinal chemistry

The benzisoxazole analogs represent one of the privileged structures in medicinal chemistry and there has been an increasing number of studies on benzisoxazole-containing compounds. The unique benzisoxazole scaffold also exhibits an impressive potential as antimicrobial, anticancer, anti-inflammatory, anti-glycation agents and so on. This review examines the state of the art in medicinal chemistry as it relates to the comprehensive and general summary of the different benzisoxazole analogs, their use as starting building blocks of multifarious architectures on scales sufficient to drive human drug trials. The number of reports describing benzisoxazole-containing highly active compounds leads to the expectation that this scaffold will further emerge as a potential candidate in the field of drug discovery.

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Reference:
Benzisoxazole – Wikipedia,
,Benzisoxazole – an overview | ScienceDirect Topics

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Application of 298-12-4, The reactant in an enzyme-catalyzed reaction is called a substrate. Enzyme inhibitors cause a decrease in the reaction rate of an enzyme-catalyzed reaction.I hope my blog about 298-12-4 is helpful to your research.

Application of 298-12-4, Enzymes are biological catalysts that produce large increases in reaction rates and tend to be specific for certain reactants and products. 298-12-4, Name is 2-Oxoacetic acid, SMILES is OC(=O)C=O, belongs to Benzisoxazole compound. In a article, author is Banu, Afshan, introduce new discover of the category.

3-{[6-(4-Chlorophenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl]methyl}-1,2-benzoxazole

In the title compound, C18H11ClN4OS, the benzisoxazole and imidazothiadiazole rings are inclined at an angle of 23.81 (7)degrees with respect to each other. The imidazothiadiazole and chlorophenyl rings make a dihedral angle of 27.34 (3)degrees. In the crystal, intermolecular C-H center dot center dot center dot N interactions generate a chain along the c axis and C-H center dot center dot center dot O interactions form centrosymmetric dimers resulting in an R-2(2)(26) graph-set motif. Moreover, the C-H center dot center dot center dot N and S center dot center dot center dot N [3.206 (4) angstrom] interactions links the molecules into R(7) ring motifs. The packing is further stabilized by pi-pi stacking interactions between the thiadiazole rings with a shortest centroid-centroid distance of 3.497 (3) angstrom. In addition, C-H center dot center dot center dot pi interactions are observed in the crystal structure

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Reference:
Benzisoxazole – Wikipedia,
,Benzisoxazole – an overview | ScienceDirect Topics

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Application of 298-12-4, Because enzymes can increase reaction rates by enormous factors and tend to be very specific, typically producing only a single product in quantitative yield, they are the focus of active research.you can also check out more blogs about 298-12-4.

Application of 298-12-4, The transformation of simple hydrocarbons into more complex and valuable products via catalytic C¨CH bond functionalisation has revolutionised modern synthetic chemistry. 298-12-4, Name is 2-Oxoacetic acid, SMILES is OC(=O)C=O, belongs to Benzisoxazole compound. In a article, author is WEPPLO, P, introduce new discover of the category.

5-ARYLOXYBENZISOXAZOLE ESTERS – SYNTHESIS AND HERBICIDAL ACTIVITY

A series of benzisoxazole glycolate and acetate ester diphenyl ethers were prepared. The preparation of intermediate 5-hydroxybenzisoxazoleacetic acid from 4,6-dihydroxycoumarin was improved by reaction in the presence of excess hydroxylamine hydrochloride. The resultant diphenyl ether herbicides were potent total vegetation control pre- and postemergence herbicides.

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Reference:
Benzisoxazole – Wikipedia,
,Benzisoxazole – an overview | ScienceDirect Topics

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But sometimes, even after several years of basic chemistry education, it is not easy to form a clear picture on how they govern reactivity! 298-12-4, you can contact me at any time and look forward to more communication. Application In Synthesis of 2-Oxoacetic acid.

Reactions catalyzed within inorganic and organic materials and at electrochemical interfaces commonly occur at high coverage and in condensed media, causing turnover rates to depend strongly on interfacial structure and composition, 298-12-4, Name is 2-Oxoacetic acid, SMILES is OC(=O)C=O, in an article , author is STIFF, DD, once mentioned of 298-12-4, Application In Synthesis of 2-Oxoacetic acid.

REDUCTIVE METABOLISM OF THE ANTICONVULSANT AGENT ZONISAMIDE, A 1,2-BENZISOXAZOLE DERIVATIVE

1. The metabolism of zonisamide in vitro was characterized through aerobic and anaerobic incubations with rat liver subcellular fractions and cultured gastrointestinal microflora. 2. Zonisamide reacted with rat hepatic microsomal cytochrome P-450 and exhibited a Type I binding spectrum. 3. Metabolism of zonisamide in vitro by hepatic subcellular fractions and cultured gastrointestinal flora produced a single metabolite, 2-(sulphamoylacetyl)-phenol (2-SMAP), by reductive cleavage of the 1,2-benzisoxazole ring. 4. The reductive metabolism of zonisamide was primarily mediated by microsomal cytochrome P-450. The soluble fraction enhanced reduction when combined with the microsomal fraction but itself possessed only weak reductive activity. 5. Reduction of zonisamide by the most enzymically active liver fractions required NADPH, was stimulated by FMN and SKF-525A, and was inhibited by CO or air, as well as by n-octylamine. 6. Unlike their involvement in the reduction of numerous nitro, azo, and N-oxide compounds, cultured aerobic and anaerobic intestinal flora were not principally involved in the reduction of zonisamide.

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Reference:
Benzisoxazole – Wikipedia,
,Benzisoxazole – an overview | ScienceDirect Topics