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1,2-Benzisoxazole Phosphorodiamidates as Novel Anticancer Prodrugs Requiring Bioreductive Activation

Several 1,2-benzisoxazole phosphorodiamidates have been designed as prodrugs of phosphoramide mustard requiring bioreductive activation. Enzymatic reduction of 1,2-benziosoxazole moiety is expected to result in the formation of imine intermediate due to the cleavage of the N-O bond. The imine should then be spontaneously hydrolyzed to a ketone metabolite, thereby facilitating base-catalyzed beta-elimination of cytotoxic phosphoramide mustard. As expected, the proposed prodrugs 4, 9, and 12 were at least 3-5-fold more potent cytotoxins than control compounds 5 and 15, which lack in the phosphoramide mustard group. Upon incubation with phenobarb-induced rat liver S-9 fraction, compounds 4, 9, and 12 underwent extensive NADPH-dependent metabolism with concomitant generation of alkylating activity under both hypoxic and oxic conditions. Corresponding ketone metabolites were detected for 9 and 15. NADPH-dependent bioreduction of 15 to its ketone metabolite 16 was located in the microsomal fraction and inhibited by SKF-525A and pCMBA. Compared with phenobarb-induced rat liver microsomal fraction, incubation of 15 with rat or human P450 reductase microsomes showed moderate generation of 16. Microsomal cytochrome P450 and/or P450 reductase appear to be involved in the reductive metabolism of 1,2-benzisoxazole moiety under hypoxic as well as oxic conditions.

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Synthesis and biological activity of a series of aryl tropanyl esters and amides chemically related to 1H-indole-3-carboxylic acid endo 8-methyl-8-azabicyclo[3.2.1]oct-3-yl ester. Development of a 5-HT4 agonist endowed with potent antinociceptive activity

A series of aryl tropanyl esters and amides related to 1H-indole-3-carboxylic acid endo 8-methyl-8-azabicyclo[3.2.1]oct-3-yl ester (ICS 205930, CAS 89565-68-4) were synthesized and evaluated for antinociceptive activity using the hot-plate test. Of these, the benzofurane-3-carboxylic ester of tropine (1) was found powerfully to increase the pain threshold, with a cholinergic mechanism of action. Despite the structural similarity with ICS 205930, the analgesia induced by 1 seems not to be due to 5-HT3 receptor interaction, and there is evidence of involvement of the central 5-HT4 receptor.

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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. Quality Control of 1,2-Benzisoxazole-3-acetic Acid

Decarboxylative aldol-type reaction of 2-(trifluoroacetyl)-1,3-diazoles with activated acetic acids

The highly electrophilic ketones 2-(trifluoroacetyl)-1,3-diazoles easily undergo a decarboxylative aldol-type reaction with activated acetic acids to afford heterocyclic trifluoromethyl-substituted alcohols bearing various functionalities. Georg Thieme Verlag Stuttgart.

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

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HETEROCYCLYL DERIVATIVES AND THEIR USE AS PROSTAGLANDIN D2 RECEPTOR MODULATORS

The present invention relates to phenyl-substituted heterocyclyl derivatives of the formula (I) wherein Z, n, m, R1, R2, R3, R4, R5, R6, R7 and R8 are as described in the description and their use as prostaglandin receptor modulators, most particularly as prostaglandin D2 receptor modulators, in the treatment of various prostaglandin-mediated diseases and disorders, to pharmaceutical compositions containing these compounds and to processes for their preparation.

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

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DOES CHLORINATION MODIFY THE AUXIN-LIKE ACTIVITY OF 1,2-BENZISOXAZOLE-3-ACETIC ACID?

The insertion of a chlorine atom in different positions of the aromatic ring did not increase the activity of benzisoxazole acetic acid, a new synthetic growth regulator, on shoot regeneration in vitro, pea stem elongation or flax root growth.This shows that this compound behaves differently from other synthetic auxins, and suggests that its activity is mainly related to the structure of its ring.Key Word Index – Chlorinated benzisoxazolic acetic acid; auxin-like activities; in vitro shoot regeneration; pea stem elongation; flax root growth.

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Benzisoxazole – Wikipedia,
Benzisoxazole – an overview | ScienceDirect Topics

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Facile preparation of protected benzylic and heteroarylmethyl amines via room temperature Curtius rearrangement

A step-wise, room temperature procedure for acyl azide formation and the subsequent Curtius rearrangement of phenyl and heteroaryl acetic acids is described. We have developed a protocol for room temperature Curtius rearrangement in MeOH or CHCl3 that provides an improvement over standard conditions, avoiding the use of additives or heat. This room temperature optimization of the Curtius rearrangement prevents the formation of side products often observed with benzylic acids, allowing access to a variety of benzylic and heteroarylmethyl amines.

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Benzisoxazole – Wikipedia,
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METHOD FOR SULFONATION OF 1,2-BENZISOXAZOLE-3-ACETIC ACID

An efficient method for the preparation of 1,2-benzisoxazole-3-methanesulfonic acid involves a reaction of 1,2-benzisoxazole-3-acetic acid in toluene with chlorosulfonic acid optionally mixed with an inert solvent in the presence of a particular Lewis base (ester or a nitrile).

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

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One of the oldest and most widely used commercial enzyme inhibitors is aspirin, category: Benzisoxazole, which selectively inhibits one of the enzymes involved in the synthesis of molecules that trigger inflammation. you can also check out more blogs about category: Benzisoxazole

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Fragment-Based Drug Discovery of Inhibitors of Phosphopantetheine Adenylyltransferase from Gram-Negative Bacteria

The discovery and development of new antibiotics capable of curing infections due to multidrug-resistant and pandrug-resistant Gram-negative bacteria are a major challenge with fundamental importance to our global healthcare system. Part of our broad program at Novartis to address this urgent, unmet need includes the search for new agents that inhibit novel bacterial targets. Here we report the discovery and hit-to-lead optimization of new inhibitors of phosphopantetheine adenylyltransferase (PPAT) from Gram-negative bacteria. Utilizing a fragment-based screening approach, we discovered a number of unique scaffolds capable of interacting with the pantetheine site of E. coli PPAT and inhibiting enzymatic activity, including triazolopyrimidinone 6. Structure-based optimization resulted in the identification of two lead compounds as selective, small molecule inhibitors of bacterial PPAT: triazolopyrimidinone 53 and azabenzimidazole 54 efficiently inhibited E. coli and P. aeruginosa PPAT and displayed modest cellular potency against the efflux-deficient E. coli DeltatolC mutant strain.

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

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Condensation reactions of various nucleophiles with 3-formylchromone

3-Formylchromones 1 are condensed with 1-(2,4-difluorophenyl-2-[1,2,4] tnazol-4-yl)ethanone in acetic anhydride to afford 3-[3-(2,4-difluoro-phenyl)-3- oxo-2-[1,2,4]triazol-4-yl)propenyl]chromon-4-ones 2. 3-Formylchromone 1 when heated with benzo[d]isoxazol-3-yl-acetic acid in dry pyridine yield 3-(2-benzo[d]isoxazol-3-yl-vinyl)chromon-4-ones 3. Further, 3-formylchromone 1 on heating with N-methylpiperizine in ethanol give 1-(2-hydroxyphenyl)-3-(4- methyl-piperazin-1-yl)propenones 4.

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