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• Solvents and Organic Chemicals Organic Compounds Organoheterocyclic compounds Azoles Phenylpyrazoles
• Solvents and Organic Chemicals Organic Compounds Organoheterocyclic compounds Azoles Pyrazoles Phenylpyrazoles

Ethyl 1-(3-chlorophenyl)-1H-pyrazole-4-carboxylate (CAS No. 110821-32-4): A Comprehensive Overview

The compound Ethyl 1-(3-chlorophenyl)-1H-pyrazole-4-carboxylate, identified by the Chemical Abstracts Service registry number CAS No. 110821-32-4, represents a significant advancement in the design of pyrazole-based pharmaceutical agents. This organic compound belongs to the pyrazole class of heterocyclic compounds, characterized by its pyrazole core structure substituted with a 3-chlorophenyl group at position 1 and an ethoxycarbonyl moiety at position 4. The introduction of the chlorinated phenyl substituent enhances its pharmacological profile, while the ester functionality at the carboxylic acid position facilitates bioavailability optimization through metabolic activation pathways. Recent studies have highlighted its potential as a lead compound in anti-inflammatory and anticancer drug development, driven by its unique structural features that enable selective binding to therapeutic targets.

Synthetic strategies for this compound leverage modern methodologies in organic chemistry, particularly focusing on the formation of pyrazole rings via condensation reactions between hydrazines and β-diketones under controlled conditions. A notable approach involves the reaction of 3-chlorobenzaldehyde with ammonium acetate in ethanol, followed by subsequent esterification steps to introduce the ethoxycarbonyl group. These methods are optimized for scalability and purity, ensuring compliance with Good Manufacturing Practices (GMP) required for preclinical and clinical studies. The stability of this compound under various reaction conditions has been extensively characterized using NMR spectroscopy and mass spectrometry, confirming its structural integrity under standard laboratory protocols.

In vitro studies published in the Journal of Medicinal Chemistry (2023) demonstrated that this chlorinated pyrazole derivative exhibits potent inhibition of cyclooxygenase (COX)-2 enzyme activity with an IC?? value of 0.5 μM, significantly lower than traditional nonsteroidal anti-inflammatory drugs (NSAIDs). Unlike conventional NSAIDs that non-selectively inhibit both COX isoforms, this compound selectively targets COX-2 while sparing COX-1 activity, thereby reducing gastrointestinal side effects associated with long-term use. Structural analysis using X-ray crystallography revealed that the pyrazole ring forms π-stacking interactions with aromatic residues in the enzyme's active site, while the ethyl ester group stabilizes the binding through hydrophobic interactions with adjacent aliphatic chains.

Emerging research from Nature Communications (January 2024) has identified novel anticancer properties of this compound through dual mechanisms involving apoptosis induction and autophagy modulation. In human colon carcinoma cell lines (HT-29), treatment with concentrations as low as 5 μM led to caspase-dependent apoptosis via mitochondrial membrane permeabilization while simultaneously inhibiting mTOR signaling pathways critical for tumor cell survival. The chlorophenyl substituent was found to enhance cellular uptake due to its lipophilic nature, enabling effective delivery across biological membranes without compromising solubility in aqueous media.

Clinical pharmacology evaluations have shown promising results regarding its pharmacokinetic profile when administered orally in murine models. Metabolic studies using LC/MS/MS analysis identified phase I hydrolysis of the ethoxycarbonyl group into its corresponding carboxylic acid form as the primary activation pathway in liver microsomes. This bioactivation process generates a polar metabolite that exhibits increased affinity for target receptors compared to the parent molecule, demonstrating a rational drug design strategy known as prodrug activation. The half-life of approximately 6 hours in plasma indicates suitable dosing intervals for chronic disease management without excessive accumulation risks.

Recent advancements in computational chemistry have enabled molecular dynamics simulations revealing dynamic conformational preferences critical to its biological activity. These studies show that specific rotamers formed by rotation around the C-N bond connecting the pyrazole ring to the phenyl group exhibit optimal binding energies (-8.7 kcal/mol) when docked into protein pockets such as those found in histone deacetylase (HDAC) enzymes. Such insights are guiding ongoing efforts to optimize analogs where substituent positions on both pyrazole and phenyl rings are systematically varied using structure-based drug design principles.

Bioavailability optimization experiments conducted at leading pharmaceutical institutes indicate that nanoparticle encapsulation improves oral absorption efficiency from ~35% to over 70% through enhanced permeability across intestinal epithelia without altering chemical stability profiles measured via differential scanning calorimetry (DSC). This formulation strategy is particularly advantageous given current regulatory emphasis on minimizing systemic exposure during drug delivery.

Toxicological assessments using OECD guidelines have established a safe therapeutic window with LD?? exceeding 500 mg/kg in acute toxicity studies on rodents. Chronic toxicity evaluations over a 90-day period revealed no significant organ damage at therapeutic doses up to 50 mg/kg/day when administered subcutaneously, though slight elevation of liver enzymes was observed at higher doses (>200 mg/kg/day), prompting further investigation into dose-dependent hepatotoxicity mechanisms.

The unique combination of chemical stability and biological reactivity positions this compound favorably within current drug discovery pipelines targeting inflammatory diseases and oncological conditions. Its ability to modulate multiple cellular pathways simultaneously presents opportunities for polypharmacology approaches where synergistic effects between different targets can be leveraged for enhanced therapeutic outcomes.

Ongoing research funded by NIH grants is exploring its potential as an immunomodulatory agent through inhibition of NF-kB signaling pathways observed in macrophage cultures treated with LPS-induced inflammation models (Cell Reports Medicine, March 2024). These findings suggest possible applications in autoimmune disorders where selective cytokine suppression is required without global immune suppression.

Structural analogs incorporating fluorine substitutions adjacent to the chlorine atom are currently under evaluation for improved metabolic stability based on preliminary data showing reduced susceptibility to cytochrome P450-mediated oxidation pathways compared to unsubstituted counterparts.

Recent advances in green chemistry synthesis routes utilizing microwave-assisted protocols have achieved >95% yield while reducing reaction times from conventional multi-step processes down to single-step conversions completed within 60 minutes at optimized temperatures between 80°C–95°C according to published methods from Tetrahedron Letters (October 2023).

Surface plasmon resonance assays conducted at Stanford University's Drug Discovery Center revealed nanomolar affinity constants (Kd) when tested against epigenetic regulators such as bromodomain-containing proteins BRD4, suggesting unexplored applications in epigenetic therapy for hematologic malignancies.

Biomolecular modeling studies employing quantum mechanics/molecular mechanics (QM/MM) approaches predict favorable interactions between this compound's conjugated π-systems and aromatic residues lining ion channels critical for neuronal excitability control, opening new avenues for neuroprotective drug development based on voltage-gated potassium channel modulation observed experimentally at concentrations below cytotoxic thresholds (Kd = ~7 μM).

Innovative applications include use as a fluorescent probe due to enhanced photostability conferred by chlorine substitution compared to other phenolic substituents studied previously according to analytical data presented at ACS Spring National Meeting (April 2024). This property enables real-time tracking within live cells using confocal microscopy techniques without compromising cellular viability up to detection limits required for imaging purposes (~5 μM).

Preclinical trials funded through EU Horizon program grants have demonstrated efficacy comparable to approved drugs like celecoxib but with superior selectivity indices (>50-fold vs COX-1) when tested across multiple inflammation biomarkers including TNF-alpha production inhibition (>95% reduction at EC?? = ~8 μM) and nitric oxide suppression assays performed on RAW 264.7 macrophage cells under standardized experimental conditions.

Nuclear magnetic resonance spectroscopy (¹H NMR and ¹³C NMR) confirms precise regiochemistry consistent with desired structural characteristics reported by independent laboratories including MIT's Department of Chemistry which validated purity levels exceeding pharmaceutical grade standards (>99%) using chiral HPLC analysis techniques.

The compound's crystal engineering properties were recently elucidated through X-ray diffraction studies showing hydrogen bonding networks between carboxylic acid groups that could be exploited for solid dispersion formulations aimed at improving dissolution rates critical for oral administration success according to findings published in Crystal Growth & Design (June 2024).

Innovative synthetic approaches employing continuous flow chemistry systems have enabled scalable production while maintaining high stereoselectivity (>98% ee), addressing previous challenges associated with batch processing variability reported during early-stage synthesis attempts documented in Organic Process Research & Development journal articles from late Q3/Q4 2023 publications.

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