6953-61-3

Usage

Uses

Used in Pharmaceutical Industry:
1-NAPHTHOHYDROXAMIC ACID is used as a histone deacetylase inhibitor for its potential therapeutic effects in treating various diseases. Its ability to inhibit specific HDAC enzymes suggests that it may play a role in modulating gene expression and cellular processes, which could be beneficial in the development of drugs for cancer, neurodegenerative disorders, and other conditions where HDAC activity is implicated.
Used in Epigenetic Research:
1-NAPHTHOHYDROXAMIC ACID is used as a research tool for studying the role of histone deacetylases in epigenetic regulation. By inhibiting specific HDAC enzymes, researchers can gain insights into the molecular mechanisms underlying gene expression changes and the potential therapeutic applications of targeting these enzymes.
Used in Drug Development:
1-NAPHTHOHYDROXAMIC ACID is used as a lead compound in the development of new drugs targeting HDAC enzymes. Its potency and selectivity for certain HDACs make it a promising candidate for further optimization and refinement to create more effective and targeted therapeutic agents.

Biochem/physiol Actions

1-Naphthohydroxamic Acid is a cell-permeable, potent, and selective histone deacetylase 8 (HDAC8) inhibitor. 1-Naphthohydroxamic acid selectively inhibits HDAC8 (IC50 = 14 μM) over class I HDAC1 and class II HDAC6 (IC50 >100 μM). Treatment of cells with 1-Naphthohydroxamic acid does not increase neither global histone H4 nor tubulin acetylation . Also in contrast to the pan-HDAC inhibitors the compound is not reducing total intracellular HDAC activity.

InChI:InChI=1/C11H9NO2/c13-11(12-14)10-7-3-5-8-4-1-2-6-9(8)10/h1-7,14H,(H,12,13)

Upstream product

• 879-18-5 naphthalene-1-carbonic acid chloride 
• 2459-24-7 methyl 1-naphthoate 
• 86-55-5 1-naphthalenecarboxylic acid 
• 4780-79-4 1-naphthalene methanol 

Downstream Products

• 134-32-7 1-amino-naphthalene 

Relevant academic research and scientific papers

Palladium-Catalyzed 5-exo-dig Cyclization Cascade, Sequential Amination/Etherification for Stereoselective Construction of 3-Methyleneindolinones

An cascade intramolecular 5-exo-dig cyclization of N-(2-iodophenyl)propiolamides and sequential amination/etherification (with N-hydroxybenzamides, phenyl hydroxycarbamate) protocol for the synthesis of amino- and phenoxy-substituted 3-methyleneindolinones using unexpensive Pd(PPh3)4 as catalyst has been developed. The protocol enables the assembly of structurally important oxindole cores featuring moderate functional group tolerance (particularly the halo group), affording a broad spectrum of products with diverse substituents in good to excellent yields. (Figure presented.).

Palladium-catalyzed cascade decarboxylative amination/6- endo-dig benzannulation of o-alkynylarylketones with n-hydroxyamides to access diverse 1-naphthylamine derivatives

An efficient and practical one-pot strategy to produce highly substituted 1-naphthylamines via sequential palladium-catalyzed decarboxylative amination/intramolecular 6-endo-dig benzannulation reactions has been described. In this reaction, a broad range of electron-rich, electron-neutral, and electron-deficient o-alkynylarylketones react well with N-hydroxyl aryl/alkylamides to give a diversity of 1-naphthylamines in good to excellent yields under mild reaction conditions. The gram-scale synthesis, with benefits such as undiminished product yield and easy transformation, illustrated the practicality of this method.

Consecutive Lossen rearrangement/transamidation reaction of hydroxamic acids under catalyst- and additive-free conditions

The Lossen rearrangement is a classic process for transforming activated hydroxamic acids into isocyanate under basic or thermal conditions. In the current report we disclosed a consecutive Lossen rearrangement/transamidation reaction in which unactivated hydroxamic acids were converted into N-substituted formamides in a one-pot manner under catalyst- and additive-free conditions. One feature of this novel transformation is that the formamide plays triple roles in the reaction by acting as a readily available solvent, a promoter for additive-free Lossen rearrangement, and a source of the formyl group in the final products. Acyl groups other than formyl could also be introduced into the product when changing the solvent to other low molecular weight aliphatic amide derivatives. The solvent-promoted Lossen rearrangement was better understood by DFT calculations, and the intermediacy of isocyanate and amine was supported well by experiments, in which the desired products were obtained in excellent yields under similar conditions. Not only monosubstituted formamides were synthesized from hydroxamic acids, but also N,N-disubstituted formamides were obtained when secondary amines were used as precursors.

A two-step tandem reaction to prepare hydroxamic acids directly from alcohols

The first synthesis of hydroxamic acids from alcohols has been developed. Both benzylic and aliphatic alcohols can be tolerated and applied in this reaction. The methodology is economical, environmentally benign and high yielding. This journal is

An efficient method for the preparation of hydroxamic acids

Reactions of acyl chlorides with hydroxylamine hydrochloride and NaHCO 3 generate the corresponding hydroxamic acid products in ethyl acetate and water at room temperature for 5 min. This is a simple and efficient method to synthesize a wide range of hydroxamic acids from carboxylic acids in excellent yield and high purity after simple post-treatment without chromatographic purification. In this process, the highlights are the simple separation of products and cheaply available reagents.

INHIBITORS FOR HDAC8

INHIBITORS FOR HDAC8 ABSTRACT OF THE DISCLOSURE This invention discloses a new HDAC inhibitor scaffold designed to exploit a unique sub-pocket of the HDAC8 active site. These compounds are based on inspection of HDAC8 crystal structures bound to various inhibitors, which showed that the HDAC8 active site is surprisingly malleable and can accommodate inhibitor structures that are distinct from the canonical "zinc-binding group-linker-cap group" structures of SAHA, TSA and similar HDAC inhibitors. Some of the new inhibitors based on this new scaffold are >100 fold selective for HDAC8 over other class I and class II HDACs with IC50 values 1μM against HDAC8. The present invention provides a new type of "linkerless" HDAC8 inhibitors and methods of treating a pathological condition using the same. Treatment of human cells with the new inhibitors of the present invention show a unique pattern of hyperacetylated proteins compared with the broad spectrum HDAC inhibitor TSA.

Design and evaluation of 'Linkerless' hydroxamic acids as selective HDAC8 inhibitors

In this report, we describe new HDAC inhibitors designed to exploit a unique sub-pocket in the HDAC8 active site. These compounds were based on inspection of the available HDAC8 crystal structures bound to various inhibitors, which collectively show that the HDAC8 active site is unusually malleable and can accommodate inhibitor structures that are distinct from the canonical 'zinc binding group-linker-cap group' structures of SAHA, TSA, and similar HDAC inhibitors. Some inhibitors based on this new scaffold are >100-fold selective for HDAC8 over other class I and class II HDACs with IC50 values 1 μM against HDAC8. Furthermore, treatment of human cells with the inhibitors described here shows a unique pattern of hyperacetylated proteins compared with the broad-spectrum HDAC inhibitor TSA.

Identification of a potent botulinum neurotoxin A protease inhibitor using in situ lead identification chemistry

Botulinum neurotoxins (BoNTs), etiological agents of the deadly food poisoning disease botulism, are the most toxic proteins currently known. By using in situ lead identification chemistry, we have uncovered the first class of inhibitors that displays nanomolar potency. From a 15 μM lead compound, structure-activity relationship studies were performed granting the most potent BoNT/A inhibitor reported to date that displays an inhibition constant of 300 nM.

Solid supported synthesis of hydroxamic acids

A novel approach to the solid supported synthesis of hydroxamic acids was developed. It employs oxime resin and unlike all previously reported methods allows for the use of acid labile protecting groups. Cleavage is induced by treatment with tert-butyldim