26673-71-2

Upstream product

• 5466-88-6 3,4-dihydro-3-oxo-2H-1,4-benzoxazine 
• 105-36-2 ethyl bromoacetate 
• 10147-68-9 N-(2-hydroxyphenyl)-2-chloroacetamide 
• 105-39-5 chloroacetic acid ethyl ester 
• 95-55-6 2-amino-phenol 
• 708262-58-2 2-bromo-N-(2-hydroxyphenyl)acetamide 

Relevant academic research and scientific papers

N′-[(E)-Arylidene]-2-(2,3-dihydro-3-oxo-4H-1,4-benzoxazin-4-yl)-acetohydrazides: Synthesis and Evaluation of Caspase Activation Activity and Cytotoxicity

In our search for novel small cytotoxic molecules potentially activating procaspase-3, we have designed and synthesized a series of novel N′-[(E)-arylidene]-2-(2,3-dihydro-3-oxo-4H-1,4-benzoxazin-4-yl)acetohydrazides (5, 6). Biological evaluation revealed that seven compounds, including 5h, 5j, 5k, 5l, 5n, 6a, and 6b, exhibited moderate to strong cytotoxicity against three human cancer cell lines (SW620, colon cancer; PC-3, prostate cancer; NCI-H23, lung cancer). Among these compounds, two most cytotoxic compounds (5h and 5j) displayed from 3- up to 10-fold higher potency than PAC-1 and 5-FU in three cancer cell lines tested. Three compounds 5j, 5k, and 5n were also found to display better caspases activation activity in comparison to PAC-1. Especially, compound 5k activated the level of caspases activity by 200% higher than that of PAC-1. From this study, three compounds 5j, 5k, and 5n could be considered as potential leads for further design and development of caspase activators and anticancer agents.

(E)-N'-ARYLIDENE-2-(3-OXO-2,3-DIHYDRO-4H-BENZO[b][1,4]OXAZIN-4-YL) ACETOHYDRAZIDES AND AN ANTICANCER COMPOSITION COMPRISING THE SAME AS AN ACTIVE INGREDIENT

The present invention relates to (E)-Nandprime;-arylidene-2-(3-oxo-2,3-dihydro-4H-benzo[b][1,4]oxazin-4-yl)acetohydrazide and an anticancer composition comprising the same as an active component. Specifically, (E)-Nandprime;-arylidene-2-(3-oxo-2,3-dihydro-4H-benzo[b][1,4]oxazin-4-yl)acetohydrazide according to the present invention activates procaspase-3 to promote the conversion to capase-3, thereby being able to be used as a proliferative inhibitor for various cancer cells. A compound according to the present invention is expected to be developed as an active component of a potent anticancer agent.COPYRIGHT KIPO 2020

Synthesis, antimicrobial, antioxidant and docking study of novel 2H-1,4-Benzoxazin-3(4H)-One derivatives

A NOVEL series of 1,4-benzoxazinone derivatives were synthesized and characterized using FT-IR , 1H-NMR, 13C-NMR and Mass spectroscopy. These compounds were in vitro screened against several bacterial species gram positive and gram negative as well as Candida albicans and found exhibiting moderate to potent activity. The antioxidant study was confirmed for the synthesized derivatives against 1,1-diphenyl-2-picryl hydrazyl (DPPH) radical. Docking study for the potent compound 8 against glucosamine-6-phosphate synthase , the target enzyme for the antimicrobial agents was explored to explain the interactions of the discovered hits with in the amino acid residues of the enzyme active side. The docking parameters enhanced the activity of new compound as promising antimicrobial agents.

Ultrasound-assisted synthesis and antimicrobial evaluation of some novel benzoxazinonylhydrazone derivatives

Some new benzoxazinonylhydrazone analogs derived from substituted benzaldehydes and benzoxazin-3(4H)-one pharmacophore have been synthesized by simple and efficient methods, using ultrasound (US) irradiations as well as conventional thermal heating (CTH).

Novel benzoxazin-3-one derivatives: Design, synthesis, molecular model-ing, anti-hiv-1 and integrase inhibitory assay

Introduction: Integrase is a validated drug target for anti-HIV-1 therapy. The second generation integrase inhibitors display π-stacking interaction ability with 3’-end nucleotide as a streamlined metal chelating pharmacophore. Method: In this study, we introduced benzoxazin-3-one scaffold for integrase inhibitory potential as bioisostere replacement strategy of 2-benzoxazolinone. Result: Molecular modeling studies revealed that amide functionality alongside oxadiazole het-eroatoms and sulfur in the second position of oxadiazole ring could mimic the metal chelating pharmacophore. The halobenzyl ring occupies hydrophobic site created by the cytidylate nucleotide (DC-16). Conclusion: The most potent and selective compound displayed 110 μM IC50 with a selectivity index of more than 2.

Synthesis and Structure–Activity Relationship Studies of Benzo[b][1,4]oxazin-3(4H)-one Analogues as Inhibitors of Mycobacterial Thymidylate Synthase X

Since the discovery of a flavin-dependent thymidylate synthase (ThyX or FDTS) that is absent in humans but crucial for DNA biosynthesis in a diverse group of pathogens, the enzyme has been pursued for the development of new antibacterial agents against Mycobacterium tuberculosis, the causative agent of the widespread infectious disease tuberculosis (TB). In response to a growing need for more effective anti-TB drugs, we have built upon our previous screening efforts and report herein an optimization campaign of a novel series of inhibitors with a unique inhibition profile. The inhibitors display competitive inhibition toward the methylene tetrahydrofolate cofactor of ThyX, enabling us to generate a model of the compounds bound to their target, thus offering insight into their structure–activity relationships.

Development of small-molecule Trypanosoma brucei N-myristoyltransferase inhibitors: Discovery and optimisation of a novel binding mode

The enzyme N-myristoyltransferase (NMT) from Trypanosoma brucei has been validated both chemically and biologically as a potential drug target for human African trypanosomiasis. We previously reported the development of some very potent compounds based around a pyrazole sulfonamide series, derived from a high-throughput screen. Herein we describe work around thiazolidinone and benzomorpholine scaffolds that were also identified in the screen. An X-ray crystal structure of the thiazolidinone hit in Leishmania major NMT showed the compound bound in the previously reported active site, utilising a novel binding mode. This provides potential for further optimisation. The benzomorpholinone was also found to bind in a similar region. Using an X-ray crystallography/structure-based design approach, the benzomorpholinone series was further optimised, increasing activity against T. brucei NMT by >1000-fold. A series of trypanocidal compounds were identified with suitable in vitro DMPK properties, including CNS exposure for further development. Further work is required to increase selectivity over the human NMT isoform and activity against T. brucei. HATs off to diversity! Screening a diverse library against Trypanosoma brucei N-myristoyltransferase (NMT) identified hits based on thiazolidinone and benzomorpholine scaffolds. X-ray crystallography of these compounds bound to Leishmania major NMT revealed novel active site binding conformations. Using the structural information, the benzomorpholine scaffold was optimised to a blood-brain barrier penetrant compound with activity against TbNMT of 0.002 μm.

Synthesis of 1,3,4-oxadiazol-2-yl-methyl-4H-benzo [1,4] oxazin-3-ones

2H-1,4-Benzoxazin-3(4H)-one (1) was treated with ethyl 2-bromoacetate in the presence of K2CO3 in DMF at 80° to obtain 3,4-dihydro-3-oxo-2H-1,4-benzoxazine-4- acetic acid ethyl ester (2). Treatment of (2) with hydrazine hydrate gave (3-oxo-2,3- dihydrobenzo [1,4] oxazin-4-yl) acetic acid hydrazide (3). Reaction of (3) with benzoyl chlorides in ethanol at RT gave N1[2-(3-oxo-2,3-dihydro benzo [1,4] oxazin-4-yl) acetyl] hydrazide (4). Treatment of (4) with p-TsCl in the presence of Et3N in dichloromethane gave benzoxazinyl-1,3,4-oxadiazoles (5) by the intramolecular cyclisation of N,N'-diacyl derivatives (4). Structures of all the new products 5a-5f are supported by their spectral data.

Synthesis, biological activity and conformational study of 1,4- benzoxazine derivatives as potassium channel modulators

With the aim of discovering new molecules with K+-channel activating properties, we have synthesized derivatives of cromakalim (CRK), an important molecule which shows specific affinity towards K+ channels, by replacing the benzopyrane ring of this reference compound with a 1,4-benzoxazine moiety. A different number of substituents showing a good discrimination between hydrophobic and electronic properties have been inserted at the 6-position of the 1,4-benzoxazine ring. We describe here the synthesis and discuss the solid state conformation of these new molecules. When tested on rat aorta ring precontracted with phenylephrine, two compounds (2c and 2d) showed a concentration-dependent relaxation similar to that measured for cromakalim but less potent than this reference drug.