6626-92-2

Basic information

• Product Name: 5-chloro-N-(2-chlorophenyl)-2-hydroxy-benzaMide
• Synonyms: Benzamide, 5-chloro-N-(2-chlorophenyl)-2-hydroxy-
• CAS NO: 6626-92-2
• Molecular Formula: C₁₃H₉Cl₂NO₂
• Molecular Weight: 282.12206
• Mol File: 6626-92-2.mol

Chemical Properties

• Melting Point: 107 °C
• Boiling Point: 358.8°Cat760mmHg
• Flash Point: 170.8°C
• Appearance: /
• Density: 1.479g/cm³
• Vapor Pressure: 1.2E-05mmHg at 25°C
• Refractive Index: 1.685
• PKA: 7.65±0.43(Predicted)
• CAS DataBase Reference: 5-chloro-N-(2-chlorophenyl)-2-hydroxy-benzaMide(CAS DataBase Reference)
• NIST Chemistry Reference: 5-chloro-N-(2-chlorophenyl)-2-hydroxy-benzaMide(6626-92-2)
• EPA Substance Registry System: 5-chloro-N-(2-chlorophenyl)-2-hydroxy-benzaMide(6626-92-2)

Safety Data

• Hazardous Substances Data: 6626-92-2(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
5-chloro-N-(2-chlorophenyl)-2-hydroxy-benzamide is used as a potential therapeutic agent for [application reason], leveraging its structural modifications from the parent compound salicylamide to explore enhanced or novel pharmacological effects.
Used in Chemical Research:
In the field of chemical research, 5-chloro-N-(2-chlorophenyl)-2-hydroxy-benzamide serves as a subject for studying the impact of structural modifications on the biological activity of salicylamide derivatives, potentially leading to the discovery of new drugs with improved properties.

InChI:InChI=1/C13H9Cl2NO2/c14-8-5-6-12(17)9(7-8)13(18)16-11-4-2-1-3-10(11)15/h1-7,17H,(H,16,18)

Upstream product

• 321-14-2 5-chloro-2-hydroxybenzoic acid 
• 95-51-2 o-chloroaniline 
• 15216-81-6 5-chloro-2-hydroxybenzoyl chloride 

Downstream Products

• 50-65-7 Niclosamide 

Relevant articles and documents

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.

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.

Reversible small molecule inhibitors of MAO A and MAO B with anilide motifs

Background: Ligands consisting of two aryl moieties connected via a short spacer were shown to be potent inhibitors of monoamine oxidases (MAO) A and B, which are known as suitable targets in treatment of neurological diseases. Based on this general blueprint, we synthesized a series of 66 small aromatic amide derivatives as novel MAO A/B inhibitors. Methods: The compounds were synthesized, purified and structurally confirmed by spectroscopic methods. Fluorimetric enzymological assays were performed to determine MAO A/B inhibition properties. Mode and reversibility of inhibition was determined for the most potent MAO B inhibitor. Docking poses and pharmacophore models were generated to confirm the in vitro results. Results: N-(2,4-Dinitrophenyl)benzo[d][1,3]dioxole-5-carboxamide (55, ST-2043) was found to be a reversible competitive moderately selective MAO B inhibitor (IC50 = 56 nM, Ki = 6.3 nM), while N-(2,4-dinitrophenyl)benzamide (7, ST-2023) showed higher preference for MAO A (IC50 = 126 nM). Computational analysis confirmed in vitro binding properties, where the anilides examined possessed high surface complementarity to MAO A/B active sites. Conclusion: The small molecule anilides with different substitution patterns were identified as potent MAO A/B inhibitors, which were active in nanomolar concentrations ranges. These small and easily accessible molecules are promising motifs, especially for newly designed multitargeted ligands taking advantage of these fragments.

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.

Structure–Function Studies on IMD-0354 Identifies Highly Active Colistin Adjuvants

Infections caused by multidrug-resistant (MDR) bacteria, particularly Gram-negative bacteria, are an escalating global health threat. Often clinicians are forced to administer the last-resort antibiotic colistin; however, colistin resistance is becoming increasingly prevalent, giving rise to the potential for a situation in which there are no treatment options for MDR Gram-negative infections. The development of adjuvants that circumvent bacterial resistance mechanisms is a promising orthogonal approach to the development of new antibiotics. We recently disclosed that the known IKK-β inhibitor IMD-0354 potently suppresses colistin resistance in several Gram-negative strains. In this study, we explore the structure–activity relationship (SAR) between the IMD-0354 scaffold and colistin resistance suppression, and identify several compounds with more potent activity than the parent against highly colistin-resistant strains of Acinetobacter baumannii and Klebsiella pneumoniae.

Identification and synthesis of low-molecular weight cholecystokinin B receptor (CCKBR) agonists as mediators of long-term synaptic potentiation

Recently, He et al. reported that CCKB receptors located in the neocortex of the brain when bound to their bound natural ligand, CCK peptides, enhance memory, bringing up the possibility that agonists targeting the CCKB receptor may act as therapeutic agents in diseases in which memory loss is marked as observed in dementia and Alzheimer’s. In this report, we describe the synthesis of novel low-molecular weight benzoamine CCKB receptor agonists. The compounds made in this series were determined to be mostly partial agonists, although some antagonists were identified, as well, capable of triggering calcium release in a cell line that overexpresses the CCKB receptor. Compound 35 demonstrated an EC50 of 0.15 μM in the cell-based assay, but more importantly, several of the compounds, including 35, demonstrated a physiological effect, inducing long-term potentiation in rat brains comparable to the CCK-8 peptide albeit at much higher concentrations. Based on these findings, benzoamines may be the basis for a new series of CCKB receptor agonists in drug-discovery efforts that seek to develop therapeutics to prevent memory loss.

CHEMICAL MODULATORS OF SIGNALING PATHWAYS AND THERAPEUTIC USE

Described are methods of treating a disease associated with dysregulation of the Wnt/Frizzled signaling pathway. The methods include identifying subjects in need of therapy, administering inhibitors of the Wnt/Frizzled signaling pathway, pharmaceutical compositions including the inhibitors, and methods of using the compounds and compositions for treating cancer, bacterial and viral infection, lupus, type II diabetes, nonalcoholic steatohepatitis (NASH) and nonalcoholic fatty liver disease (NAFLD) in a subject.

Structure-activity studies of Wnt/β-catenin inhibition in the Niclosamide chemotype: Identification of derivatives with improved drug exposure

The Wnt signaling pathway plays a key role in regulation of organ development and tissue homeostasis. Dysregulated Wnt activity is one of the major underlying mechanisms responsible for many diseases including cancer. We previously reported the FDA-approved anthelmintic drug Niclosamide inhibits Wnt/β-catenin signaling and suppresses colon cancer cell growth in vitro and in vivo. Niclosamide is a multi-functional drug that possesses important biological activity in addition to inhibition of Wnt/β-catenin signaling. Here, we studied the SAR of Wnt signaling inhibition in the anilide and salicylamide region of Niclosamide. We found that the 4′-nitro substituent can be effectively replaced by trifluoromethyl or chlorine and that the potency of inhibition was dependent on the substitution pattern in the anilide ring. Non-anilide, N-methyl amides and reverse amide derivatives lost significant potency, while acylated salicylamide derivatives inhibited signaling with potency similar to non-acyl derivatives. Niclosamide's low systemic exposure when dosed orally may hinder its use to treat systemic disease. To overcome this limitation we identified an acyl derivative of Niclosamide, DK-520 (compound 32), that significantly increased both the plasma concentration and the duration of exposure of Niclosamide when dosed orally. The studies herein provide a medicinal chemical foundation to improve the pharmacokinetic exposure of Niclosamide and Wnt-signaling inhibitors based on the Niclosamide chemotype. The identification of novel derivatives of Niclosamide that metabolize to Niclosamide and increase its drug exposure may provide important research tools for in vivo studies and provide drug candidates for treating cancers with dysregulated Wnt signaling including drug-resistant cancers. Moreover, since Niclosamide is a multi-functional drug, new research tools such as DK520 could directly result in novel treatments against bacterial and viral infection, lupus, and metabolic diseases such as type II diabetes, NASH and NAFLD.