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Structurally Diverse Mitochondrial Branched Chain Aminotransferase (BCATm) Leads with Varying Binding Modes Identified by Fragment Screening

Inhibitors of mitochondrial branched chain aminotransferase (BCATm), identified using fragment screening, are described. This was carried out using a combination of STD-NMR, thermal melt (Tm), and biochemical assays to identify compounds that bound to BCATm, which were subsequently progressed to X-ray crystallography, where a number of exemplars showed significant diversity in their binding modes. The hits identified were supplemented by searching and screening of additional analogues, which enabled the gathering of further X-ray data where the original hits had not produced liganded structures. The fragment hits were optimized using structure-based design, with some transfer of information between series, which enabled the identification of ligand efficient lead molecules with micromolar levels of inhibition, cellular activity, and good solubility.

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Reference£º
Benzisoxazole – Wikipedia,
Benzisoxazole – an overview | ScienceDirect Topics

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Process for the preparation of zonisamide

The present invention provides an improved process for the preparation of zonisamide or a derivative thereof comprising (a) reacting 1,2-benzisoxazole-3-methane-sulfonic acid with a halogenating agent in a first organic solvent to provide benzisoxazole methane sulfonyl halide; and, (b) reacting benzisoxazole methane sulfonyl halide with an amine in a second organic solvent to form zonisamide or a derivative thereof.

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Reference£º
Benzisoxazole – Wikipedia,
Benzisoxazole – an overview | ScienceDirect Topics

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Catalysts function by providing an alternate reaction mechanism that has a lower activation energy than would be found in the absence of the catalyst. In a patent, 4865-84-3, molecular formula is C9H7NO3, introducing its new discovery. Safety of 1,2-Benzisoxazole-3-acetic Acid

Synthesis and antimicrobial studies of novel methylene bridged benzisoxazolyl imidazo[2,1-b][1,3,4]thiadiazole derivatives

Novel methylene bridged benzisoxazolyl imidazo[2,1-b][1,3,4]thiadiazoles (3a-f) were synthesized from benzisoxazolyl-3-acetic acid and thiosemicarbazide. Reaction of 3 with bromine in glacial acetic acid in the presence of anhydrous sodium acetate yielded the corresponding 5-bromo derivatives (4a-f). While compound 3 furnished the 5-nitroso derivatives (5a-f) on refluxing with sodium nitrite solution. Thiocyanato derivatives (6a-f) were obtained by treating the imidazothiadiazole 3 with bromine and potassium thiocyanate in glacial acetic acid at room temperature. The structures of the newly synthesized compounds were confirmed by IR, NMR, mass and elemental analysis. All the compounds were screened for their antibacterial and antifungal activities. Some of the compounds displayed very good antibacterial and antifungal activity.

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Reference£º
Benzisoxazole – Wikipedia,
Benzisoxazole – an overview | ScienceDirect Topics

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BENZISOXAZOLE DERIVATIVES AS POTASSIUM CHANNEL MODULATORS FOR THE TREATMENT OF E.G. RESPIRATORY DISEASES, EPILEPSY AND CONVULSIONS

This invention relates to novel benzisoxazole derivatives that are found to be potent modulators of potassium channels and, as such, are valuable candidates for the treatment of diseases or disorders as diverse as those which are responsive to the modulation of potassium channels e.g. a respiratory disease, epilepsy or convulsions. X represents a subsituent selected from the group consisting of CO-NR”R””, CO-O-R”, CO-NH-S, CO-NH-SO2R”””, CO-NH-C=N, SO2-NR”R””, 2,3-dihydro-1-H-tetrazol-5-yl and [1, 2, 4]oxadiazolidin-5-one; wherein R” and R””, independently of each other, represent hydrogen or alkyl or phenyl; and R””” represents alkyl, cycloalkyl, haloalkyl or phenyl, which phenyl may optionally be substituted one or more times with substituents selected from halo, trifluoromethyl, trifluoromethoxy, cyano and nitro.

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Reference£º
Benzisoxazole – Wikipedia,
Benzisoxazole – an overview | ScienceDirect Topics

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Synthesis and Herbicidal Activities of 1,2-Benzisoxazole-3-acetamide Derivatives

Many 1,2-benzisoxazole-3-acetamides were synthesized and their herbicidal activities in the paddy field were studied.Of the compounds tested, N-alpha,alpha-dimethylbenzyl-2-bromo-(1,2-benzisoxazol-3-yl)acetamide 10a was the most effective.Details of the synthesis and the results of herbicidal evaluations are given.

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Reference£º
Benzisoxazole – Wikipedia,
Benzisoxazole – an overview | ScienceDirect Topics

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Cytokinin-like activity of N,N?-diphenylureas. N,N?-bis-(2,3-methylenedioxyphenyl)urea and N,N?-bis-(3,4-methylenedioxyphenyl)urea enhance adventitious root formation in apple rootstock M26 (Malus pumila Mill.)

Vegetative propagation of cuttings is a widespread method to multiplicate plants. Adventitious root formation is a key step in vegetative propagation and considerable progress has recently been made in understanding root formation. But, in spite of the efforts made, no new rooting treatments have been developed. Here, we report for the first time, that N,N?-bis-(2,3-methylenedioxyphenyl)urea and N,N?-bis-(3,4-methylenedioxyphenyl)urea enhance adventitious root formation in microcuttings of Malus pumila Mill. rootstock M26. Roots emerge without auxin supplementation in the darkness, transfer in hormone free medium, or callus formation. With the use of different bioassays, we also demonstrate that these two diphenylurea derivatives do not show cytokinin- or auxin-like activity.

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Reference£º
Benzisoxazole – Wikipedia,
Benzisoxazole – an overview | ScienceDirect Topics

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AUXIN-LIKE ACTIVITY OF 1,2-BENZISOXAZOLE-3-ALKANOIC ACIDS

A series of benzisoxazole-alkanoic acids, differing in the length of the side-chain, have been synthesized and their activity tested on pea stem elongation, flax root growth and shoot regeneration from tomato cotyledon explants.All compounds had little or no effect on cell elongation or root growth, but a stimulating effect on shoot induction in vitro, thus showing that their activity, like that of 1,2-benzisoxazole acetic acid. is partly independent of the side-chain and is linked to the structure of the benzisoxazole ring. – Key words: 1,2-Benzisoxazole-3-alkanoic acids; auxin-like activity; pea stem elongation; flax root growth; in vitro shoot generation.

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Reference£º
Benzisoxazole – Wikipedia,
Benzisoxazole – an overview | ScienceDirect Topics

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NEW OXABISPIDINE COMPOUNDS FOR THE TREATMENT OF CARDIAC ARRHYTHMIAS

There is provided compounds of formula I, [Chemical formula should be inserted here. Please see paper copy] wherein R1 to R4 , R41 to R46 and Z have meanings given in the description, which are useful in the prophylaxis and in the treatment of arrhythmias, in particular atrial and ventricular arrhythmias

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Reference£º
Benzisoxazole – Wikipedia,
Benzisoxazole – an overview | ScienceDirect Topics

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Docking studies of some 2-(benzo[d] isoxazole-3-yl)-N-(oxothiazolidine) derivative with COX-II and thromboxane as target protein and evaulation of its anti inflammatory activty

A scaffold of ten thiazolidinone derivatives of 1,2-Benzisoxazole [5a-5j] were synthesized using 4-Hydroxy-2H-chromen-2-one as the starting material. The synthesis was carried out by conventional technique and the synthesized compounds were identified by physical methods and their structures characterized by spectral analysis. The identified compounds were further subjected to docking studies using two proteins, COX-2 and thromboxane which are known as mediators of inflammation. All the compounds showed good docking scores indicating that they are potent inhibitors of COX-2 and thromboxane. In line with the above result, invitro anti-inflammatory studies were carried out on the moieties by HRBC membrane stabilization method using diclofenac as standard. Significant anti-inflammatory activity was observed in compounds 5a, 5b, 5c, 5f, 5g and 5i.

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Reference£º
Benzisoxazole – Wikipedia,
Benzisoxazole – an overview | ScienceDirect Topics

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METHODS FOR HAIR FOLLICLE STEM CELL PROLIFERATION

The present invention relates to compositions of Sonic Hedgehog (Shh) pathway activators and Wnt agonists and methods of using them to induce self-renewal of hair follicle stem cells, including inducing the hair follicle stem cells to proliferate while maintaining, in the daughter cells, the capacity to differentiate into hair follicle epithelial cells.

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Reference£º
Benzisoxazole – Wikipedia,
Benzisoxazole – an overview | ScienceDirect Topics