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Zonisamide is a 1.2 benzisoxazole derivative and the first agent of this chemical class to be developed as an antiepileptic dry. It has shown activity in various animal models of epilepsy, and although a detailed mode of action awaits clarification it appears to block the propagation/spread of seizure discharges and to suppress the epileptogenic focus. Clinical experience with zonisamide in Japan has documented its efficacy in the treatment of partial seizures (partial-onset generalised tonic-clonic, simple partial and/or complex partial seizures), and to a more variable extent, generalised tonic-clonic, generalised tonic (mainly seen in symptomatic generalised epilepsies including Lennox-Gastaut Syndrome) and compound/combination seizures (including those refractory to treatment with other antiepileptic drugs). Other generalised seizure types have also responded to therapy with zonisamide, although only small patient numbers were studied. Zonisamide has demonstrated efficacy equivalent to that of carbamazepine in patients with (mainly) partial seizures, and to that of valproic acid in a small study of children (n = 32) with generalised seizures. Animal studies suggest that zonisamide possesses a more favourable therapeutic index than most other antiepileptic drugs. However, clinical trials conducted to date, have not confirmed any overt tolerability advantage. Indeed, whereas the recommended therapeutic plasma zonisamide concentration is 20 mg/L, clinical investigations have associated adverse events with plasma zonisamide concentrations of >30 mg/L. suggesting the usefulness of therapeutic drug monitoring. Moreover, although plasma concentrations of zonisamide are empirically regarded to be proportional to therapeutic doses in patients in Japan, nonlinear pharmacokinetics have been reported for this drug in patients in the US and may further complicate its use in this patient population. Additional pharmacokinetic studies will help to establish the change in pharmacokinetic profile that occurs with dosage titration in patients outside Japan. Among 700 patients treated with zonisamide in Europe/US, a high incidence of renal calculi (1.9%) has been noted however, the causal relationship to zonisamide is disputed. Indeed, although urinary lithiasis has also been recorded for patients in Japan, the aetiology, incidence and spontaneous regression of this condition suggest that it is not a serious problem for this patient population. Until this difference is clarified, it is likely that zonisamide will find its greatest use in the treatment of patients in Japan. Like many other established antiepileptic drugs, available data suggest the propensity for zonisamide to alter the pharmacokinetic profile of other anticonvulsant agents, although severe interactions appear to be unlikely. The ultimate positioning of zonisamide in the therapy of epilepsy awaits clearer definition of its pharmacokinetic, efficacy (particularly in comparison with other antiepileptics) and tolerability profiles. At present therefore, available data do not support the use of this drug in individuals outside of Japan, except in formal clinical studies involving careful monitoring. However, for patients in Japan with epilepsies refractory to established therapy, zonisamide would appear a valid alternative, particularly in the treatment of partial seizures.

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

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We tested the morphogenetic and cell elongating activity of 1,2-benzisoxazole-3-one, a compound similar to 1,2-benzisoxazole-3-acetic acid but lacking the lateral carbon chain. For comparison, we tested also the activity of indole-2,3-dione, having the same indolic ring as indole-3-acetic acid but no lateral carbon chain. The tests were made on the regeneration of tomato (Lycopersicon esculentum Miller var. Alice) from cotyledons and on pea (Pisum sativum L. var. Alaska) stem elongation. We found that 1,2-benzisoxazole-3-one retains part of the high shoot inducing activity of 1,2-benzisoxazole-3-acetic acid, while indole-2,3-dione is inactive. Both compounds have no effect on root induction or cell elongation. It seems therefore that the activity of 1,2-benzisoxazole-3-acetic acid is partly related to the structure of its ring, and that also in this respect 1,2-benzisoxazole-3-acetic acid differs from other auxin-like compounds.

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

The Shocking Revelation of ((1R,4S)-7,7-Dimethyl-2-oxobicyclo[2.2.1]heptan-1-yl)methanesulfonic acid

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Benzisoxazole-3-acetic acid, a new synthetic growth regulator, was administered to protoplast cultures from Nicotiana tabacum and subsequently to the developed microcalluses, to test its activity on plant regeneration from protoplasts in different culture conditions. Such activity, compared to that of naphthalene-acetic acid, proved to be rather low in the stage of cellular division and microcallus formation but particulary high in the stage of shoot induction from microcallus, thus confirming that the activity of this compound is mainly morphogenetic.

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

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A practical synthesis of benzisoxazole 1 and its conversion to alpha-aryloxyisobutyric acid 2 using 1,1,1-trichloro-2-methyl-2-propanol (chloretone) was developed. Benzisoxazole I was formed in high yields by the action of either methanesulfonyl chloride/base upon intermediate oxime 8 or with thionyl chloride/base, which initially forms cyclic sulfite 10. A highly reactive, short-lived intermediate derived from chloretone was detected by ReacIR and its half-life determined to be similar to 5 min. Reaction conditions for the Bargellini reaction were developed that resulted in a 95% yield of 2 from the reaction of highly hindered phenol 1 with chloretone hemihydrate and powdered NaOH in acetone. Thus highly hindered alpha-aryloxyisobutyric acids can be made in a single step in high yield.

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

Our Top Choice Compound: 929-59-9

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Polyampholyte latexes that contain 29/18 and 25/23 mol % of (styrylmethyl)trimethylammonium/methacrylate units and styrene cross-linked with divinylbenzene are colloidally stable in 4 M NaCl solution. As catalytic media in basic solutions 0.5 mg mL(-1) of the polyampholyte latexes increase the rate of decarboxylation of 6-nitrobenzisoxazole-3-carboxylate (6-NBIC) 60-115 times, while the precursor polycation latexes increase the rate 540-670 times the rate in water alone. The latexes are active catalysts in 0.67 M NaCl solution, but activity decreases as the concentration of added NaCl increases. Analysis of rate constants at varied particle concentrations indicates that the fractions of the 6-NBIC anions bound to particles are similar in the two types of latexes and that the differences in activity are due primarily to larger intraparticle rate constants in the polycation latexes than in the polyampholytes.

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

More research is needed about 52356-01-1

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A simple and efficient method for the synthesis of 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole hydrochloride is achieved. This reaction involves hydroxylamine sulfate/KOH mediated, in situ generated oxime formation and its subsequent internal cyclisation followed by alkaline hydrolysis of N-protected ketone in one step. Synthesis of 1,2-benzisoxazole analogues is described and they are found to be potent acetylcholinesterase inhibitors.

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

New explortion of 6-Hydroxyhexanoic acid

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Background: Privileged structures are potentially able to bind to a diverse range of biologically important proteins with high affinities, thus benefiting the discovery of novel bioactive compounds. 1,2-Benxisoxazole derivatives can be such important types of privileged structures possessing a rich diversity of biological properties especially in the area of CNS disorders. Methods: This review seeks to explore the most significant examples of 1,2-benzisoxazoles as privileged structures in terms of polypharmacology at the molecular level, specifically focusing on four 1,2-benzisoxazoles (zonisamide, risperidone, paliperidone, and iloperidone) which have been in clinical use and established as effective therapeutics. Furthermore, an updated and detailed account of the pharmacological properties of 1,2-benzisoxazole derivatives as therapeutics for CNS disorders is described. And finally, outlooks on current issues and future directions in this field are also provided. Results: 1,2-Benzisoxazole was successfully employed in the discovery and development of zonisamide for the treatment of epilepsy and Parkinson’s disease. 1,2-Benzisoxazole is also a significantly important structure for the development of atypical antipsychotics. Conclusion: It is very reasonable to say that 1,2-benzisoxazole is a good example of a privileged structure because it forms the centerpiece of small molecule chemical entities with a wide range of pharmacological properties, especially in the area of CNS disorders.

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

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

What Kind of Chemistry Facts Are We Going to Learn About (R)-2-Hydroxysuccinic acid

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The developed method was employed in the synthesis of medicinally important compounds and intermediates in the organic synthesis. Herein we report a variety of novel N-chloro derivatives of benzisoxazole, benzimidazoles and several other N-chloro derivatives using 1.2 equivalents of calcium hypochlorite. The process does not require any additives like acids or bases and produced moderate to excellent yields of desired products under mild conditions.

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

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The title benzisoxazole (3) is prepared isomerically pure by condensation of 2-(diethoxymethyl)cyclohexanone with hydroxylamine hydrochloride.

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