Heterocyclic Building Blocks-Benzisoxazole

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THE METABOLISM AND EXCRETION OF RISPERIDONE AFTER ORAL-ADMINISTRATION IN RATS AND DOGS

The metabolism and excretion of risperidone (RIS; 3-[2-[4-(6-fluoro-1,2-benzisoxazole-3-yl)-1-piperidinyl]ethyl]-6,7,8,9-tetrahydro-2- methyl-4H-pyrido[1,2-a]pyrimidin-4-one), a novel antipsychotic drug, were studied after single po administration of radiolabeled RIS to rats and dogs. In rats, the excretion of the radioactivity was very rapid. The predominant excretion in rat feces (78-82% of the dose) was related to an extensive biliary excretion of metabolites (72-79% of the dose), only a small part of which underwent enterohepatic circulation. In dogs, about 92% of the dose had been excreted after one week, and the fractions recovered in the urine and feces were comparable. Only a few percent of a po dose was excreted as unchanged RIS in rats as well as in dogs. Major metabolic pathways of RIS in rats and dogs were the same as those in humans. The main pathway was the hydroxylation at the alicyclic part of the 6,7,8,9-tetrahydro-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one moiety. The resulting 9-hydroxy-risperidone (9-OH-RIS) was the main metabolite in the excreta of dogs. In rats, the metabolism was more extensive, resulting in dihydroxy-RIS and hydroxy-keto Rls, which were eliminated mainly via the bile. However, in male and in female rats, just as in dogs and humans, the active metabolite 9-OH-RIS was by far the main plasma metabolite. Other major metabolic pathways were the oxidative dealkylation at the piperidine nitrogen and the scission of the isoxazole in the benzisoxazole ring system. The latter pathway appeared to be effected primarily by the intestinal microflora. The mass balance of the metabolites of RIS in dogs was dose independent from 0.05 to 1.25 mg/kg and was similar to that in humans.

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

Career opportunities within science and technology are seeing unprecedented growth across the world, and those who study chemistry or another natural science at university now have increasingly better career prospects. In a document, author is Sobieszek, G, introducing its new discovery. Application of 625-08-1.

Zonisamide: A new antiepileptic drug

Although the significant progress in pharmacotherapy of epilepsy during last decade was achieved, about one third of patients are resistant to the current treatment. When the monotherapy is not efficient, the polytherapy should be applied. Zonisamide (ZNS) is a new antiepileptic drug (AED) efficient in treating refractory epilepsy. Its efficacy in different types of seizures was confirmed in various animal studies as well as in clinical conditions. ZNS inhibits voltage-dependent Na+ channels and Ca2+ channels of T-type. The drug influences also monoamine neurotransmission and exhibits free radical scavenging properties. ZNS has a linear and favorable pharmacokinetics with excellent oral bioavailability. Furthermore, ZNS treatment, compared to other anticonvulsants, is relatively safe and well tolerated. Since ZNS is often used in polytherapy, its interactions with other AEDs seem to be of particular importance. However, the experimental data are rather inconsistent and further studies are necessary to elucidate exact effects of co-administration of ZNS with other AEDs. Recently, the clinical and experimental studies have suggested, some new indications for ZNS administration, as mania, neuropathic pain, Parkinson’s disease or migraine prophylaxis. Nowadays, it is also well established that ZNS exerts neuroprotective properties.

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

Some examples of the diverse research done by chemistry experts include discovery of new medicines and vaccines, improving understanding of environmental issues, and development of new chemical products and materials. In a document, author is BALDAN, B, introducing its new discovery. Formula: https://www.ambeed.com/products/57-11-4.html.

A STAGE-SPECIFIC BLOCK IS PRODUCED IN CARROT SOMATIC EMBRYOS BY 1,2-BENZISOXAZOLE-3-ACETIC ACID

1,2-Benz-isoxazol-3-acetic acid is slightly toxic to unorganized growing carrot cells and completely prevents somatic embryogenesis beyond the globular stage. Its action is time dependent: if added early, it affects the determination of the early stages; if added later, after determination has occurred, it has practically no effect. The blocked forms can evolve, in the presence of the compound, creating secondary embryos that, in turn, are arrested at the globular stage. Since the secondary embryos adhere to the primary ones, irregular polyembryonic masses of typical appearance are created. The internal structures of the blocked globular embryos were examined and were shown to be enlarged, vacuolized and detached from the central cells. The protoderm also displayed an altered appearance. These data, when considered together with the effects of the compound on rooting and callus formation, suggest that benz-isoxazol acetic acid acts as a weak auxin.

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

Research speed reading in 2021. Chemistry, like all the natural sciences, begins with the direct observation of nature— in this case, of matter. COA of Formula: https://www.ambeed.com/products/25383-99-7.html, 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. 25383-99-7, Name is Sodium 2-((2-(stearoyloxy)propanoyl)oxy)propanoate, molecular formula is C24H43NaO6. In an article, author is Chen, Cheng-yi,once mentioned of 25383-99-7.

A Divergent and Selective Synthesis of Isomeric Benzoxazoles from a Single N-Cl Imine

A divergent and regioselective synthesis of either 3-substituted benzisoxazoles or 2-substituted benzoxazoles from readily accessible ortho-hydroxyaryl N-H ketimines is described. The reaction proceeds in two distinct pathways through a common N-Cl imine Intermediate: (a) N-O bond formation to form benzisoxazole under anhydrous conditions and (b) NaOCl mediated Beckmann-type rearrangement to form benzoxazole, respectively. The reaction path also depends on the electronic nature of the aromatic ring, with the electron-rich aromatic rings favoring the rearrangement and the electron-deficient rings favoring the N-O bond formation. A Beckmann-type rearrangement mechanism via net [1,2]-aryl migration for the formation of 2-substituted benzoxazole is proposed.

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

New discoveries in chemical research and development in 2021.HPLC of Formula: https://www.ambeed.com/products/719-64-2.html, 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. 719-64-2, Name is 5-Chloro-3-phenylbenzo[c]isoxazole, molecular formula is C13H8ClNO. In an article, author is Jankovic, Slobodan M.,once mentioned of 719-64-2.

Evaluation of zonisamide for the treatment of focal epilepsy: a review of pharmacokinetics, clinical efficacy and adverse effects

Introduction: Zonisamide is a benzisoxazole with 3-methanesulfonamide side chain, chemically unrelated with other anticonvulsants, and approved as mono-therapy of newly diagnosed focal epilepsy with or without secondary generalization in adults or adjunctive therapy in the treatment of partial seizures, with or without secondary generalization, in adults, adolescents, and children aged 6 years and above. Areas covered: Pharmacokinetics, clinical efficacy, and the adverse effects of zonisamide are discussed in the article. The discussion is based on data from published preclinical studies, clinical trials, observational studies, systematic reviews, and approved summary of product characteristics. Expert opinion: Zonisamide is an anticonvulsant with multiple mechanisms of action on neuronal tissue, which achieves seizure freedom in more than 80% of patients with newly-onset focal epilepsy and in 6.2 to 18.1% of patients with focal onset seizures inadequately controlled by first-line anticonvulsants. Within the recommended dose range, it follows linear kinetic of elimination; it is metabolized in the liver by two cytochrome isoforms, so pharmacokinetic interactions are rare and with little clinical significance. Up to 10% of patients taking zonisamide will have problems with weight loss and more than 10% with irritability, confusion or depression, and long-lasting therapy may cause renal calculi in 1.2% of patients.

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

In chemical reaction engineering, simulations are useful for investigating and optimizing a particular reaction process or system., Recommanded Product: 868-14-4, Introducing a new discovery about 868-14-4, Name is Potassium hydrogen tartrate, molecular formula is C4H5KO6, belongs to benzisoxazole compound. In a document, author is Naumov, P.

Latent photochromism (pseudothermochromism) and photofatigue of crystalline 2-(2 ‘,4 ‘-dinitrobenzyl)pyridine

Along with the metastable 2-(2,4′-dinitrophenylmethylidene)-1,2-dihydropyridine (NH) and the unstable 6-aci-nitro-2-nitro-5-(2-pyridylmethylene)-1,3-cyclohexadiene (OH), the stable form of 2-(2′,4′-dinitrobenzyl)pyridine (DNBP), CH, is photochemically converted into small amounts of 1,2-bis(2′,4-dinitrophenyl)-1,2-bis(2′-pyridyl)ethane, trans-bis[5-nitro-2-(pyridine-2-carbonyl)phenyl]diazene N-oxide, 6-nitro-3-(2’-pyridyl)-2,1-benzisoxazole and 3-nitropyrido[1,2-b]quinolin-6-ium-11-olate. The latent photochromism of DNBP, as shown by x-ray analysis of the structures of the side-products and ESR/IR measurements, is attributed to open-shell reactions that are initiated by hydrogen photoabstraction and subsequent creation of two monoradicals, NH. and OH.. Large amounts of the radicals (ca 50% NH. and 70% OH) confined in the crystalline interior are persistent under ambient conditions. Through quasi-periodic reactions, the remaining radicals partially recover the ground-state isomers CH, NH and OH, or decay to the side-products, which results in crystalline photofatigue. Together with proton tunneling from the excited CH, the radical reactions represent dominant mechanism for the creation of NH and OH in the low-temperature regimes, but are successfully competed by the closed-shell reactions at higher temperatures. The precursor state, whose existence was assumed previously from transient absorption spectroscopy, may be identified as the radical OH.. The present work represents the first study of the photofatigue of a 2-(2,4-dinitrobenzyl)pyridine compound and extends the ‘classical’ mechanism of the photochromic reactions of nitrobenzylpyridines with a set of open-shell radical reaction routes. Copyright (C) 2004 John Wiley Sons, Ltd.

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

Chemistry, like all the natural sciences, begins with the direct observation of nature— in this case, of matter. 532-32-1, Name is Sodium benzoate, SMILES is O=C([O-])C1=CC=CC=C1.[Na+], in an article , author is Gopalsamy, Ariamala, once mentioned of 532-32-1, Electric Literature of 532-32-1.

Discovery of benzisoxazoles as potent inhibitors of chaperone heat shock protein 90

Heat shock protein 90 (Hsp90) is a molecular chaperone that is responsible for activating many signaling proteins and is a promising target in tumor biology. We have identified small-molecule benzisoxazole derivatives as Hsp90 inhibitors. Crystallographic studies show that these compounds bind in the ATP binding pocket interacting with the Asp93. Structure based optimization led to the identification of potent analogues, such as 13, with good biochemical profiles.

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

When developing chemical systems it’s of course important to gain a deep understanding of the chemical reaction process. 427-49-6, Name is alpha-Cyclopentylmandelic Acid, SMILES is O=C(O)C(O)(C1CCCC1)C2=CC=CC=C2, in an article , author is Chaker, Aida, once mentioned of 427-49-6, Quality Control of alpha-Cyclopentylmandelic Acid.

New 3-substituted-2,1-benzisoxazoles: Synthesis and antimicrobial activities

A new series of 3-substituted-2,1-benzisoxazoles (anthranils) were prepared by different methods and characterized by spectroscopic methods and mass spectrometry. These 2,1-benzisoxazoles were tested in vitro for their antiplasmodial activity on a chloroquine-resistant strain of Plasmodium falciparum (P.f.) (FcB1), and for antimicrobial activity against representative bacterial and fungal strains, as well as for cytotoxicity on MCF7 human breast cancer cells. Given the log P-calc and selectivity index values (cytotoxicity/antiplasmodial activity ratio), the benzo[c] isoxazol-3- ylmethylene-phenyl-amine (11) (imino-benzisoxazole) was identified as the best hit against P.f. (FcB1), and the benzo[c] isoxazol-3-yl-phenyl-methanone (3) (3-acyl-2,1-benzisoxazole) against P.f. and the Geotrichum candidum fungal strain. (c) 2013 Production and hosting by Elsevier B.V. on behalf of King Saud University.

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

Chemistry involves the study of all things chemical – chemical processes, chemical compositions and chemical manipulation – in order to better understand the way in which materials are structured, how they change and how they react in certain situations, Electric Literature of 40052-13-9.

Monitoring of zonisamide in human breast milk and maternal plasma by solid-phase extraction HPLC method

An HPLC method was developed for the determination of zonisamide in human breast milk and plasma. Chromatographic separation was achieved using a Develosil CN analytical column with potassium dihydrogenphosphate buffer (pH 3.5 with milk, pH 2.5 with plasma)-acetonitrile as the mobile phase. Zonisamide and 1,2-benzisoxazole-3-methansulfonamine acetate as internal standard were detected by ultraviolet absorbance at 240 nm. Zonisamide in breast milk and plasma was extracted by a rapid and simple procedure based on C-18 bonded-phase extraction. Determination of zonisamide in human breast milk and plasma was possible in the concentration range 0.05-20.0 mu g/mL. The recoveries of zonisamide added to human breast milk and plasma were 79.5-85.0% and 86.3-93.1%, respectively, with coefficients of variation of less than 8.3% and 11.4% respectively. The mean concentrations of zonisamide in breast milk and plasma were 9.41 +/- 0.95 and 10.13 +/- 0.45 mu g/mL, respectively. The average ratio between the breast milk concentration and plasma concentration (M/P ratio) was 0.93 +/- 0.09. Copyright (C) 1999 John Wiley & Sons, Ltd.

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

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