10558-45-9

Upstream product

• 15216-81-6 5-chloro-2-hydroxybenzoyl chloride 
• 615-66-7 2-chloro-p-phenylenediamine 
• 50-65-7 Niclosamide 

Downstream Products

• 1428328-99-7 N-( 4-acetylamino-2-chlorophenyl)-5-chloro-2-hydroxybenzamide 

Relevant academic research and scientific papers

Niclosamide quantification in methyl-β-cyclodextrin after derivatization to aminoniclosamide

A fluorescence derivatization method for the quantification of the anthelmintic drug niclosamide in organized media (methyl-β-cyclodextrin) is described. The derivatization reaction is based on a 3 h reduction reaction of the nitro group in niclosamide to an amino group by hydrogenation catalyzed by Pd/C in methanol:ethyl acetate (1:3). The aminoniclosamide exhibits a maximum of fluorescence at 431 nm (excitation at 280 nm) that is markedly enhanced when methyl-β-cyclodextrin is present. The methodology was assessed by the analysis of pure and dosage forms. The method showed a linear range between 0 and 2200 μg L-1 with a limit of detection of 45.7 nL and a precision (relative standard deviation) of 4.1% in niclosamide. The effect of various interferents, such as niclosamide, fructose and 2-cyano-6- metoxybenzothiazole, in several tolerance ratios, was investigated respected to aminoniclosamide.

Development of a micelle-enhanced high-throughput fluorometric method for determination of niclosamide using a microplate reader

The present paper describes the development and validation of a simple and sensitive micelle-enhanced high-throughput fluorometric method for the determination of niclosamide (NIC) in 96-microwell plates. The proposed method is based on the reduction of the nitro group of niclosamide to an amino group using Zn/HCl to give a highly fluorescent derivative that was developed simultaneously and measured at λem 444?nm after excitation at λex 275?nm. Tween-80 and carboxymethylcellulose (CMC) have been used as fluorescence enhancers and greatly enhanced the fluorescence by factors of 100–150%. The different experimental conditions affecting the fluorescence reaction were carefully investigated and optimized. The proposed method showed good linearity (r2≥?0.9997) over the concentration ranges of 1–5 and 0.5–5 μg/ml with lower detection limits of 0.01 and 0.008?μg/ml and lower quantification limits of 0.04 and 0.03?μg/ml on using Tween-80 and or CMC, respectively. The developed high-throughput method was successfully applied for the determination of niclosamide in both tablets and spiked plasma. The capability of the method for measuring microvolume samples made it convenient for handling a very large number of samples simultaneously. In addition, it is considered an environmentally friendly method with lower consumption of chemicals and solvents.

Application of niclosamide and analogs as small molecule inhibitors of Zika virus and SARS-CoV-2 infection

Zika virus has emerged as a potential threat to human health globally. A previous drug repurposing screen identified the approved anthelminthic drug niclosamide as a small molecule inhibitor of Zika virus infection. However, as antihelminthic drugs are generally designed to have low absorption when dosed orally, the very limited bioavailability of niclosamide will likely hinder its potential direct repurposing as an antiviral medication. Here, we conducted SAR studies focusing on the anilide and salicylic acid regions of niclosamide to improve physicochemical properties such as microsomal metabolic stability, permeability and solubility. We found that the 5-bromo substitution in the salicylic acid region retains potency while providing better drug-like properties. Other modifications in the anilide region with 2′-OMe and 2′-H substitutions were also advantageous. We found that the 4′-NO2 substituent can be replaced with a 4′-CN or 4′-CF3 substituents. Together, these modifications provide a basis for optimizing the structure of niclosamide to improve systemic exposure for application of niclosamide analogs as drug lead candidates for treating Zika and other viral infections. Indeed, key analogs were also able to rescue cells from the cytopathic effect of SARS-CoV-2 infection, indicating relevance for therapeutic strategies targeting the COVID-19 pandemic.

SALICYLAMIDE DERIVATIVES AND RELATED METHODS OF MAKING

Certain embodiments describe antiviral compounds and related methods of using such compounds.

Aluminum Metal-Organic Framework-Ligated Single-Site Nickel(II)-Hydride for Heterogeneous Chemoselective Catalysis

The development of chemoselective and heterogeneous earth-abundant metal catalysts is essential for environmentally friendly chemical synthesis. We report a highly efficient, chemoselective, and reusable single-site nickel(II) hydride catalyst based on robust and porous aluminum metal-organic frameworks (MOFs) (DUT-5) for hydrogenation of nitro and nitrile compounds to the corresponding amines and hydrogenolysis of aryl ethers under mild conditions. The nickel-hydride catalyst was prepared by the metalation of aluminum hydroxide secondary building units (SBUs) of DUT-5 having the formula of Al(μ2-OH)(bpdc) (bpdc = 4,4′-biphenyldicarboxylate) with NiBr2 followed by a reaction with NaEt3BH. DUT-5-NiH has a broad substrate scope with excellent functional group tolerance in the hydrogenation of aromatic and aliphatic nitro and nitrile compounds under 1 bar H2 and could be recycled and reused at least 10 times. By changing the reaction conditions of the hydrogenation of nitriles, symmetric or unsymmetric secondary amines were also afforded selectively. The experimental and computational studies suggested reversible nitrile coordination to nickel followed by 1,2-insertion of coordinated nitrile into the nickel-hydride bond occurring in the turnover-limiting step. In addition, DUT-5-NiH is also an active catalyst for chemoselective hydrogenolysis of carbon-oxygen bonds in aryl ethers to afford hydrocarbons under atmospheric hydrogen in the absence of any base, which is important for the generation of fuels from biomass. This work highlights the potential of MOF-based single-site earth-abundant metal catalysts for practical and eco-friendly production of chemical feedstocks and biofuels.

Substituted N-(4-amino-2-chlorophenyl)-5-chloro-2-hydroxybenzamide analogues potently inhibit respiratory syncytial virus (RSV) replication and RSV infection-associated inflammatory responses

Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infection in young children, and specific treatment for RSV infections remains unavailable. We herein reported a series of substituted N-(4-amino-2-chlorophenyl)-5-chloro-2-hydroxybenzamide analogues as potent RSV inhibitors. Among them, six low cytotoxic compounds (11, 12, 15, 22, 26, and 28) have been identified and selected to study associated inhibitory mechanisms. All these compounds suppressed not only the viral replication but also RSV-induced IRF3 and NF-κB activation and associated production of cytokines/chemokines. The two most potent compounds (15 and 22) were selected for further molecular mechanism studies associated with their suppression effect on RSV-activated IRF3 and NF-κB. These two compounds decreased RSV-induced IRF3 phosphorylation at serine 396 and p65 phosphorylation at serine 536 at both early and late infection phases. In addition, compound 22 also inhibited RSV-induced p65 phosphorylation at serine 276 at the late phase of RSV infection.

Discovery of Novel Substituted N-(4-Amino-2-chlorophenyl)-5-chloro-2-hydroxybenzamide Analogues as Potent Human Adenovirus Inhibitors

An effective therapy for human adenovirus (HAdV) infections in immunocompromised patients and healthy individuals with community-Acquired pneumonia remains an unmet medical need. We herein reported a series of novel substituted N-(4-Amino-2-chlorophenyl)-5-chloro-2-hydroxybenzamide analogues as potent HAdV inhibitors. Compounds 6, 15, 29, 40, 43, 46, 47, and 54 exhibited increased selectivity indexes (SI > 100) compared to the lead compound niclosamide, while maintaining sub-micromolar to low micromolar potency against HAdV. The preliminary mechanistic studies indicated that compounds 6 and 43 possibly target the HAdV DNA replication process, while compounds 46 and 47 suppress later steps of HAdV life cycle. Notably, among these derivatives, compound 15 showed improved anti-HAdV activity (IC50 = 0.27 μM), significantly decreased cytotoxicity (CC50 = 156.8 μM), and low in vivo toxicity (maximum tolerated dose = 150 mg/kg in hamster) as compared with niclosamide, supporting its further in vivo efficacy studies for the treatment of HAdV infections.

STAT3 TRANSCRIPTION FACTOR INHIBITORS AND METHODS OF USING THE SAME

Compounds that inhibit the activity of Signal transducer and activator of transcription 3 (STAT3), or pharmaceutically acceptable salts or prodrugs thereof, and methods of using these compounds to treat cancer and other diseases.

Benzoylaniline compound and application of benzoylaniline compound in preparation of sensitizer of P.aeruginosa inhibitor

The invention discloses a benzoylaniline compound. The benzoylaniline compound has a structural general formula shown in the specification. The invention also discloses application of the benzoylaniline compound in preparation of a sensitizer of a P.aeruginosa inhibitor or in preparation of a medicine for preventing or treating bacterial infection diseases caused by P.aeruginosa. The invention also discloses an application of niclosamide in preparation of a sensitizer of a P.aeruginosa inhibitor or in preparation of a medicine for preventing or treating bacterial infection diseases caused by P.aeruginosa. The benzoylaniline compound provided by the invention can be used as a medicine for treating and/or preventing bacterial infection diseases caused by P.aeruginosa.

Highly selective transfer hydrogenation of functionalised nitroarenes using cobalt-based nanocatalysts

Anilines are important feedstock for the synthesis of a variety of chemicals such as dyes, pigments, pharmaceuticals and agrochemicals. The chemoselective catalytic reduction of nitro compounds represents the most important and prevalent process for the manufacture of functionalized anilines. Consequently, the development of selective catalysts for the reduction of nitro compounds in the presence of other reducible groups is a major challenge and is crucial. In this regard, herein we show that the cobalt oxide (Co3O4-NGr@C) based nano-materials, prepared by the pyrolysis of cobalt-phenanthroline complexes on carbon constitute highly selective catalysts for the transfer hydrogenation of nitroarenes to anilines using formic acid as a hydrogen source. Applying these catalysts, a series of structurally diverse and functionalized nitroarenes have been reduced to anilines with unprecedented chemo-selectivity tolerating halides, olefins, aldehyde, ketone, ester, amide and nitrile functionalities.