5941-13-9

Usage

Uses

Used in Pharmaceutical Research:
4,N-Dihydroxy-benzamide is utilized as a building block in organic synthesis and pharmaceutical research for its potential antioxidant and anti-inflammatory properties. It aids in the development of new therapeutic agents targeting various health conditions.
Used in Neurodegenerative Disease Treatment:
In the medical field, 4,N-Dihydroxy-benzamide is studied for its potential use in the treatment of neurodegenerative diseases. Its neuroprotective effects make it a promising candidate for further research and development in this area.

InChI:InChI=1/C20H26Cl2N4O4S/c1-29-10-4-8-23-19(27)16-13-31-17(24-16)12-26(9-5-11-30-2)20(28)25-15-7-3-6-14(21)18(15)22/h3,6-7,13H,4-5,8-12H2,1-2H3,(H,23,27)(H,25,28)

Upstream product

• 99-76-3 methyl 4-hydroxylbenzoate 
• 732308-76-8 N-(benzyloxy)-4-hydroxybenzamide 
• 103522-74-3 C₁₄H₁₃NO₃ 
• 1486-51-7 p-(benzyloxy)benzoic acid 
• 32122-11-5 4-benzyloxy-benzoic acid methyl ester 
• 99-96-7 4-hydroxy-benzoic acid 

Downstream Products

• 80694-34-4 [Fe(4-hydroxybenzoic hydroxamate)₃] 
• 96471-71-5 oxo hydroxo bis-(4-hydroxy benzhydroxamato) vanadium (V) 

Relevant academic research and scientific papers

Thioether-Directed NiH-Catalyzed Remote γ-C(sp3)-H Hydroamidation of Alkenes by 1,4,2-Dioxazol-5-ones

A NiH-catalyzed thioether-directed cyclometalation strategy is developed to enable remote methylene C-H bond amidation of unactivated alkenes. Due to the preference for five-membered nickelacycle formation, the chain-walking isomerization initiated by the NiH insertion to an alkene can be terminated at the γ-methylene site remote from the alkene moiety. By employing 2,9-dibutyl-1,10-phenanthroline as the ligand and dioxazolones as the reagent, the amidation occurs at the γ-C(sp3)-H bonds to afford the amide products in up to 90% yield (>40 examples) with remarkable regioselectivity (up to 24:1 rr).

A general concept for the introduction of hydroxamic acids into polymers

Hydroxamic acids (HA) form stable complexes with a large variety of metal-ions, affording hydroxamates with high complexation constants. Hydroxamic acid moieties play a crucial role in the natural iron metabolism. In this work, 1,4,2-dioxazoles linked to a hydroxyl group are introduced as key compounds for the installation of hydroxamic acids at synthetic polymers in well-defined positions. A general synthetic scheme is developed that gives access to a series of novel functional key building blocks that can be universally used to obtain hydroxamic acid-based monomers and polymers, for instance as protected HA-functional initiators or for the synthesis of a variety of novel HA-based monomers, such as epoxides or methacrylates. To demonstrate the excellent stability of the dioxazole-protected hydroxamic acids, direct incorporation of the dioxazole-protected hydroxamic acids into polyethers is demonstrated via oxyanionic polymerization. Convenient subsequent deprotection is feasible under mild acidic conditions. α-Functional HA-polyethers, i.e. poly ethylene glycol, polypropylene glycol and polyglycerol based on ethylene oxide, propylene oxide and ethoxy ethyl glycidyl ether, respectively are prepared with low dispersities (-1. Water-soluble hydroxamic acid functional poly(ethylene glycol) (HA-PEG) is explored for a variety of biomedical applications and surface coating. Complexation of Fe(iii) ions, coating of various metal surfaces, enabling e.g., solubilization of FeOx nanoparticles by HA-PEGs, are presented. No impact of the polyether chain on the chelation properties was observed, while significantly lower anti-proliferative effects were observed than for deferoxamine. HA-PEGs show the same complexation behavior as their low molecular weight counterparts. Hydroxamic acid functional polymers are proposed as an oxidatively stable alternative to the highly established catechol-based systems.

Histone deacetylases inhibitor and use thereof

The present invention relates to a novel histone deacetylase (HDAC) inhibitor and a medical use thereof. More specifically, it is confirmed that a novel aspirin derivative inhibits the activity of HDAC by bonding to a substrate bonding pocket of HDAC and significantly increases the acetylation of intracellular andalpha;-tubulin and histone H3, thereby exhibiting an effect of inhibiting cancer cell proliferation. The novel aspirin derivative is provided as HDAC inhibitors, thereby being able to be provided as a therapeutic agent effective for HDAC-related cancer diseases and central nervous system diseases.COPYRIGHT KIPO 2020

Aspirin-inspired acetyl-donating HDACs inhibitors

Aspirin is one of the oldest drugs for the treatment of inflammation, fever, and pain. It is reported to covalently modify COX-2 enzyme by acetylating a serine amino acid residue. By virtue of aspirin’s acetylating potential, we for the first time developed novel acetyl-donating HDAC inhibitors. In this study, we report the design, synthesis, in silico docking study, and biological evaluation of acetyl-donating HDAC inhibitors. The exposure of MDA-MB-231 cells with compound 4c significantly promotes the acetylation of α-tubulin and histone H3, which are substrates of HDAC6 and HDAC1, respectively. In silico docking simulation also indicates that compound 4c tightly binds to the deep substrate-binding pocket of HDAC6 by coordinating the active zinc ion in a bidentate manner and forming hydrogen bond interactions with Ser531 and His573 amino acid residues. In particular, compound 4c (GI50 = 147?μM) affords the significant enhancement of anti-proliferative effect on MDA-MB-231 cells, compared with its parent compound 2c (GI50 > 1000?μM) and acetyl-donating group deficient compound 6 (GI50 = 554?μM). Overall, compound 4c presents a novel strategy for developing acetyl-donating HDAC inhibitors.

Benzoic hydroxamate-based iron complexes as model compounds for humic substances: Synthesis, characterization and algal growth experiments

A series of monomeric and dimeric FeIII complexes bearing benzoic hydroxamates as O,O-chelates has been prepared and characterized by elemental analysis, IR spectroscopy, UV-Vis spectroscopy, electrospray ionization mass spectrometry (ESI-MS), cyclic voltammetry, EPR spectroscopy and for some examples by X-ray diffraction analysis. The stability of the synthesized complexes in pure water and seawater was monitored over 24 h by means of UV-Vis spectrometry. The ability to release iron from the synthesized model complexes has been investigated with algae growth experiments.

Inhibitors of the FEZ-1 metallo-β-lactamase

Metallo-β-lactamases (MBLs) catalyze the hydrolysis of β-lactams including penicillins, cephalosporins and carbapenems. Starting from benzohydroxamic acid (1) structure-activity studies led to the identification of selective inhibitors of the FEZ-1 MBL, e.g., 2,5-substituted benzophenone hydroxamic acid 17 has a Ki of 6.1 ± 0.7 μM against the FEZ-1 MBL but does not significantly inhibit the IMP-1, BcII, CphA or L1 MBLs.

Synthesis of hydroxy- and amino-substituted benzohydroxamic acids: Inhibition of ribonucleotide reductase and antitumor activity

Benzohydroxamic acids inhibit mammalian ribonucleotide reductase and exhibit antineoplastic activity in L1210 leukemic mice. Five new hydroxy- and amino-substituted benzohydroxamic acids (3,4- and 3,5-OH,3,4-NH2, 2,3,4-, and 3,4,5-OH) were prepared and tested along with 12 previously reported benzohydroxamic acids (BHA) for enzyme inhibition and antitumor activity. The most potent enzyme inhibitor in this series was 2,3,4-OH-BHA (ID50=3.5 μM), which is 140 times more potent than hydroxyurea, but its toxicity limited the antitumor activity to a 30% increase in life span of L1210 bearing mice at 125 (mg/kg) day ip for 8 days. The most effective antitumor agent in this series was 3,4-OH-BHA which prolonged the life span of L1210 bearing mice 103% at 600 (mg/kg)/day ip for 8 days.