2086-26-2

Usage

Uses

Used in Analytical Chemistry:
O-(4-NITROBENZYL)HYDROXYLAMINE HYDROCHLORIDE is used as a derivatization agent for reducing sugars in order to enhance their detection through ultraviolet absorption in high-performance liquid chromatography (HPLC) analyses. This application is particularly useful in the field of biochemistry and pharmaceutical research, where the accurate identification and quantification of reducing sugars are essential.
Used in Pharmaceutical Research:
In the pharmaceutical industry, O-(4-NITROBENZYL)HYDROXYLAMINE HYDROCHLORIDE is used as a strong UV chromophore for the derivatization of reducing sugars. This process aids in the detection and analysis of these sugars, which are crucial components in the development and testing of various drugs and medications.
Used in Biochemical Research:
O-(4-NITROBENZYL)HYDROXYLAMINE HYDROCHLORIDE is employed as a derivatization agent in biochemical research, where it helps in the detection of reducing sugars through ultraviolet absorption in HPLC analyses. This application is vital for understanding the role of these sugars in various biological processes and their potential impact on human health.

Preparation

To a solution of 25 gm (0.183 mole) of benzohydroxamic acid in 28 ml of ethanol and 10.2 gm (0.184 mole) of potassium hydroxide in 40 ml of water is added a hot solution of 39.4 gm (0.184 mole) of p-nitrobenzyl bromide in ethanol. The mixture is then heated under a reflux condenser for 45 min and cooled. The precipitated crystals are separated and crystallized from ethanol. (No yield reported.) A solution of 15 gm (0.055 mole) of the above o-p-nitrobenzylbenzohy-droxamic acid (p-nitrobenzyl benzohydroxamate) in 125 ml of hot ethanol is heated to reflux for 25 min with 150 ml of cone, hydrochloric acid. To prevent the precipitation of the final product during the work-up, the following steps are carried out rapidly. The clear solution is diluted with 150 ml of water and while still warm benzoic acid and other by-products are separated by extraction with 200 ml of chloroform. The aqueous layer is evaporated to dryness under reduced pressure to afford a crude yield of 10.75 gm (96%). The residue is recrys-tallized from hot 2 Ν hydrochloric acid and washed in turn with ethanol and with ether to afford a solid, m.p. 217°C. The free base may be produced by neutralizing the salt with sodium carbonate solution; O-p-nitrobenzylhydroxylamine, m.p. 56°C (recrystal-lized from petroleum ether). By a similar technique, O-allylhydroxylamine hydrochloride, m.p. 172°C (dec.) was also prepared. An examination of the product of butylating benzohydroxamic acid showed that a nonacidic fraction and an equal weight of an acidic fraction were readily isolated. The nonacidic fraction contained mainly Ο, Ο '-dibutyl benzohydroxi-mate (b.p. 175-180°C/13 mm Hg) and some aniline (probably formed during the reaction by a Lossen rearrangement). On hydrolysis with eth-anolic hydrochloric acid, the hydroximate produced ethyl benzoate and O-butylhydroxylamine hydrobromide (m.p. 159-161°C; hydrochloride, m.p. 156-157°C). The acidic fraction contained mainly O-butylbenzohydroxamic acid (butyl benzohydroxamate) which on hydrolysis formed O-butylhydrox-ylamine hydrochloride and benzoic acid. It has been contended that in this particular work, the presence of an Ν,Ο-dibutylbenzohy-droxamic acid had been overlooked. The major source of O-butylhy-droxylamine hydrochloride is from the acidic fraction, although the yield is not particularly high. The initial preparation of the butylated benzohydroxamic acid deriva-tives has been repeated recently. The analysis of the reaction products by vapor-phase chromatography showed it to contain 43% of O-butyl-benzohydroxamic acid (butyl benzohydroxamate), 17% of iV,0-dibutyl-benzohydroxamic acid, and 8% of n-butyl(Z)-0-n-butylbenzohydroximate: The nature of the remaining 32% of the crude reaction product was not determined. The use of benzohydroxamic acid has been extended to the preparation of a variety of O-substituted hydroxylamines. For example, halocarboxylic acids have been used as alkylating agents to produce α-aminooxy acids of the type, NH20(CH2)?C02H. A variety of O-benzylhydroxylamines, O-aralkylhydroxylamines, as well as simpler O-substituted hydroxylamines have also been prepared. In some of these prepara-tions, the hydrolysis of the O-substituted benzohydroxamic acid was car-ried out with hot alcoholic hydrogen chloride. This treatment evidently prevented the O-N cleavage which had been observed during the aqueous hydrolysis of the substituted benzohydroxamic acids.

InChI:InChI=1/C7H8N2O3/c8-12-5-6-1-3-7(4-2-6)9(10)11/h1-4H,5,8H2

Upstream product

• 64583-54-6 N-Benzoyl-O-p-nitrobenzylhydroxylamine 
• 1944-96-3 O-(p-nitrobenzyl)hydroxylamine 
• 100-14-1 4-nitrobenzyl chloride 
• 619-73-8 4-nitrobenzyl chloride 
• 100-11-8 1-bromomethyl-4-nitro-benzene 
• 30777-85-6 N-phthalimido-O-(p-nitrobenzyl)-hydroxylamine 

Downstream Products

• 31150-87-5 p-Nitrobenzyloxy-harnstoff 
• 132778-58-6 4-(4-Nitro-benzyloxy)-allophansaeure-4-nitro-benzylester 
• 189261-36-7 3-(4-nitrobenzyloximino)hexahydroazepin-2-one 
• 100-14-1 4-nitrobenzyl chloride 
• 931406-25-6 1,3,2',2''',6'''-pentakis-[N-(tert-butoxycarbonyl)]-6',5''-dideoxy-5''-[N-(4-nitrobenzyloxy)imino]paromomycin 

Relevant academic research and scientific papers

Palladium-catalyzed regio- And stereoselective access to allyl ureas/carbamates: Facile synthesis of imidazolidinones and oxazepinones

Typically, transition metal catalysis enforces the stereodefined outcome of a reaction. Here we disclose the palladium-catalyzed regio- and stereoselective access to allylic ureas/carbamates and their further exploitation to diverse cyclic structures under operationally simple reaction conditions. This protocol features palladium-catalyzed decarboxylative amidation of highly modular VECs with good to excellent yield, minimal waste production, wide substrate scope, and low catalyst loading. In follow-up chemistry, we demonstrated the debenzylation of vinylic imidazolidinones to N-hydroxycyclic ureas and regioselective derivatization towards the facile synthesis of halohydrins and oxiranes under mild reaction conditions in good to excellent yields. This journal is

Design, synthesis and evaluation of oxime-functionalized nitrofuranylamides as novel antitubercular agents

A series of oxime-functionalized nitrofuranylamides were designed, synthesized and evaluated for their in vitro anti-mycobacterial activities against MTB H37Rv and drug-resistant clinical isolates. Among them, two compounds 7a and 7b exhibited excellent activity against the three tested strains. Both of them were comparable to the first-line anti-TB agents INH and RIF against MTB H37Rv, and were far more potent than INH and RIF against MDR-TB 16833 and 16995 strains. Thus, both of them could act as leads for further optimization.

O-benzyl-N-(9-acridinyl)hydroxylamines

A series of O-benzyl-N-(9-acridinyl)hydroxylamines was prepared, isolated, and evaluated for biological activity using both thermal denaturation and MTT assays. Changes in the thermal denaturation temperature of genomic calf-thymus DNA ranged from +6.6 °C to +20.2 °C. MTT assays on SNB-19 glioblastoma cells provided biological activity that ranged from 17.4 μM to 33.2 μM. Both evaluation methods of biological activity indicate that substitution of the benzyl group by either electron-withdrawing or electron-donating groups provides a measureable benefit in these assays. The two assays agreed on the magnitude of the interaction for each substitution pattern.

O-alkylhydroxylamines as rationally-designed mechanism-based inhibitors of indoleamine 2,3-dioxygenase-1

Indoleamine 2,3-dioxygenase-1 (IDO1) is a promising therapeutic target for the treatment of cancer, chronic viral infections, and other diseases characterized by pathological immune suppression. Recently important advances have been made in understanding IDO1's catalytic mechanism. Although much remains to be discovered, there is strong evidence that the mechanism proceeds through a heme-iron bound alkylperoxy transition or intermediate state. Accordingly, we explored stable structural mimics of the alkylperoxy species and provide evidence that such structures do mimic the alkylperoxy transition or intermediate state. We discovered that O-benzylhydroxylamine, a commercially available compound, is a potent sub-micromolar inhibitor of IDO1. Structure-activity studies of over forty derivatives of O-benzylhydroxylamine led to further improvement in inhibitor potency, particularly with the addition of halogen atoms to the meta position of the aromatic ring. The most potent derivatives and the lead, O-benzylhydroxylamine, have high ligand efficiency values, which are considered an important criterion for successful drug development. Notably, two of the most potent compounds demonstrated nanomolar-level cell-based potency and limited toxicity. The combination of the simplicity of the structures of these compounds and their excellent cellular activity makes them quite attractive for biological exploration of IDO1 function and antitumor therapeutic applications.

NOVEL VASCULAR LEAKAGEAGE INHIBITOR

The present disclosure relates to a novel vascular leakage inhibitor. The novel vascular leakage inhibitor of the present invention inhibits the apoptosis of vascular endothelial cells, inhibits the formation of actin stress fibers induced by VEGF, and enhances the cortical actin ring structure, thereby inhibiting vascular leakage. Accordingly, the vascular leakage inhibitor of the present invention can prevent or treat various diseases caused by vascular leakage. Since the vascular leakage inhibitor of the present invention is synthesized from commercially available or easily synthesizable pregnenolones, it has remarkably superior feasibility of commercial synthesis.

4-Alkyloxyimino-cytosine nucleotides: Tethering approaches to molecular probes for the P2Y6 receptor

4-Alkyloxyimino derivatives of pyrimidine nucleotides display high potency as agonists of certain G protein-coupled P2Y receptors (P2YRs). In an effort to functionalize a P2Y6R agonist for fluorescent labeling, we probed two positions (N4 and γ-phosphate of cytidine derivatives) with various functional groups, including alkynes for click chemistry. Functionalization of extended imino substituents at the 4 position of the pyrimidine nucleobase of CDP preserved P2Y6R potency generally better than γ-phosphoester formation in CTP derivatives. Fluorescent Alexa Fluor 488 conjugate 16 activated the human P2Y6R expressed in 1321N1 human astrocytoma cells with an EC50 of 9 nM, and exhibited high selectivity for this receptor over other uridine nucleotide-activated P2Y receptors. Flow cytometry detected specific labeling with 16 to P2Y 6R-expressing but not to wild-type 1321N1 cells. Additionally, confocal microscopy indicated both internalized 16 (t1/2 of 18 min) and surface-bound fluorescence. Known P2Y6R ligands inhibited labeling. Theoretical docking of 16 to a homology model of the P2Y6R predicted electrostatic interactions between the fluorophore and extracellular portion of TM3. Thus, we have identified the N4-benzyloxy group as a structurally permissive site for synthesis of functionalized congeners leading to high affinity molecular probes for studying the P2Y6R.

NON-STEROIDAL COMPOUNDS

The present invention relates to non-steroidal compounds useful in the treatment of inflammatory conditions and pharmaceutical compositions comprising them. A representative example of these compounds is formula (III).

Synthesis and fungicidal activity of macrolactams and macrolactones with an oxime ether side chain

Three series of novel macrolactams and macrolactones - 12-alkoxyimino- tetradecanlactam, 12-alkoxyiminopentadecanlactam, and 12-alkoxyiminodecanlactone derivatives (7A, 7B, and 7C) - were synthesized from corresponding 12-oxomacrolactams and 12-oxomacrolactone. Their structures were confirmed by 1H NMR and elemental analysis. The Z and E isomers of 7A and 7B were separated, and their configurations were determined by 1H NMR. These compounds showed fair to excellent fungicidal activities against Rhizoctonia solani Kuehn. It is interesting that the Z and E isomers of most of the compounds have quite different fungicidal activities. The fact that the compounds have a gradual increase of fungicidal activity in the order of 7A, 7C, and 7B indicated that the macrocyclic derivatives with a hydrogen-bonding acceptor (=N-O-) and a hydrogen-bonding donor (-CONH-) on the ring, and a three methylenes distance (CH2CH2CH2) between these two functional groups, exhibited the best fungicidal activity. The bioassay also showed that 7B not only has good fungicidal activity but also may have a broad spectrum of fungicidal activities.

New calcium antagonists: Synthesis, X-ray analysis, and smooth muscle relaxing effect of 3-[O-(benzyl-substituted)-oximino-ethers]-hexahydroazepin-2,3-diones

A series of new Z and E 3-[O-(benzyl-substituted)-oximino-ether]-hexahydroazepin-2,3-diones was prepared from the corresponding hexahydroazepin-2,3-diones and examined as smooth muscle relaxants. E and Z structures were assigned by NMR analysis and confirmed for 16 (E and Z) by an X-ray diffraction using synchrotron radiations. The nitrobenzyl derivative 16 was the most potent in vitro as relaxant of rat trachea precontracted with acetylcholine. The E isomer 16b was more potent than the Z isomer 16a. E isomer 16b is more potent than aminophylline to relax both rat trachea and human bronchus.This derivative acts mainly by inhibiting cellular infux of extracellular calcium since it inhibits potently and dose-dependently the contractions of rat trachea to high concentrations of KCl and to CaCl2 in a depolarizing medium. It appears to act weakly by inducing cGMP and cAMP synthesis. Moreover, its relaxing activity is not related to an inhibition of phosphodiesterases, to opening of potassium channels or to induction of prostaglandin synthesis. Therefore, 16b appears to work mainly as a potent calcium antagonist. (C) 1999 Elsevier Science Ltd.

Reactions of N-Acyl-O-arylhydroxylamines: Part IV - Preparation of Some N-Arylsulphonyl-O-arylhydroxylamines

A number of N-arylsulphonyl-O-alkylhydroxylamines (III) have been prepared by condensing appropriate alkoxyamines with arylsulphonyl chlorides in the presence of a base.The alkoxyamines have been obtained from the corresponding alkoxyamine hydrochlorides or hydrobromides (II) which in turn have been prepared by the hydrolysis of appropriate N-benzoyl-O-alkylhydroxylamines (I) with ethanolic hydrogen chloride or hydrogen bromide.The structure assignments of III are based on elemental analyses, chemical reaction and spectral (IR, PMR) data.