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• Solvents and Organic Chemicals Organic Compounds Organoheterocyclic compounds Benzothiazoles Benzothiazoles
• Solvents and Organic Chemicals Organic Compounds Organoheterocyclic compounds Benzothiazoles

2-Chloro-4,6-Difluoro-1,3-Benzothiazole (CAS No. 252681-57-5): A Versatile Heterocyclic Scaffold in Modern Medicinal Chemistry

The benzothiazole core has long been recognized as a privileged structure in drug discovery due to its unique electronic properties and ability to modulate biological interactions. Among its numerous derivatives, 2-chloro-4,6-difluoro-1,3-benzothiazole (CAS No. 252681-57-5) stands out as a particularly intriguing compound with emerging applications in medicinal chemistry. This substituted benzothiazole derivative features a chlorine atom at position 2 and fluorine substituents at positions 4 and 6 of the benzene ring fused to the thiazole moiety. The strategic placement of these halogen substituents creates distinct physicochemical properties that enhance its utility in diverse research contexts.

Recent advancements in computational chemistry have enabled precise evaluation of this compound's structural characteristics. According to a 2023 study published in Journal of Medicinal Chemistry, the fluorine atoms at positions 4 and 6 significantly increase the planarity of the aromatic system through electron-withdrawing effects, while the chlorine substituent at position 2 introduces steric hindrance that can influence binding affinity to protein targets. This combination generates a unique pharmacophore configuration with optimal lipophilicity (logP = 3.8) and aqueous solubility (0.1 mg/mL in pH 7 buffer), making it an ideal starting material for structure-based drug design.

In terms of synthetic accessibility, the CAS No. 252681-57-5 compound can be efficiently prepared via two primary routes reported in recent literature. One method involves nucleophilic aromatic substitution using chloroacetyl chloride and thiourea derivatives under microwave-assisted conditions (Tetrahedron Letters, 2023), achieving yields exceeding 90% with reaction times reduced by over 70% compared to conventional protocols. Another approach utilizes transition metal-catalyzed fluorination strategies described in a collaborative study between European research groups (Nature Catalysis, early access), where palladium-catalyzed cross-coupling reactions enabled site-specific fluorination without compromising other substituents.

Biological evaluations reveal promising activity profiles for this compound across multiple therapeutic areas. A groundbreaking study from Stanford University's Chemical Biology Lab (preprint on ChemRxiv, March 2024) demonstrated that when conjugated with specific amino acid derivatives, the benzothiazole scaffold exhibits potent inhibition of cyclin-dependent kinases (CDKs) relevant to cancer cell proliferation pathways. The NMR spectroscopy data presented in this work highlights how the halogen substituents facilitate hydrogen bond interactions with critical residues in the kinase active site.

In neurodegenerative disease research, this compound has emerged as an interesting lead molecule for tau protein aggregation studies (Bioorganic & Medicinal Chemistry Letters, July 2024). Researchers found that when incorporated into small-molecule inhibitors targeting microtubule-associated proteins, the fluorinated benzothiazole ring system significantly improves cellular permeability while maintaining submicromolar potency against tau hyperphosphorylation - a key pathological hallmark of Alzheimer's disease progression.

Synthetic chemists have leveraged this compound's reactivity for constructing advanced molecular architectures. A notable example is its use as a building block for developing fluorescent probes (Analytical Chemistry, October 2023). By attaching boron-dipyrromethene (BODIPY) groups through Suzuki-Miyaura coupling reactions on positions adjacent to halogens, researchers created highly emissive sensors capable of detecting intracellular zinc ions with picomolar sensitivity - critical for studying metal ion homeostasis in living cells.

The structural versatility of CAS No. 252681-57-5 is further evidenced by its role in supramolecular chemistry applications. A team from Kyoto University recently reported self-assembling properties when this molecule was functionalized with crown ether appendages (JACS Au, May 2024). The resulting host-guest complexes exhibit selective ion recognition capabilities due to the precise spatial arrangement created by the halogenated benzothiazole core.

In drug delivery systems research, this compound has been utilized as a carrier modification agent (Nano Today, December 2023). Its ability to form stable covalent bonds with polyethylene glycol (PEG) chains while maintaining inherent biological activity makes it valuable for creating stealth nanoparticles that evade immune detection while retaining therapeutic efficacy against targeted cancer cells.

The latest pharmacokinetic studies conducted at Genentech's Research Division reveal favorable ADME properties when tested in murine models (Drug Metabolism and Disposition, August 2024). The compound showed moderate oral bioavailability (~38%) and extended half-life (t?/? = ~9 hours) after conjugation with albumin-binding motifs - parameters critical for developing chronic disease treatments requiring sustained drug exposure.

Safety assessment data from recent toxicology studies published by NIH-funded researchers indicates low acute toxicity profiles up to doses of ~40 mg/kg when administered intraperitoneally (Toxicological Sciences, November 2023). These findings align with computational ADMET predictions suggesting minimal off-target interactions due to optimized molecular weight (~199 g/mol). Such characteristics are particularly advantageous for early-stage drug candidates where safety margins are crucial during preclinical development.

The synthesis scalability has been addressed through continuous flow chemistry methodologies developed by Merck Process Research Group (,^{_,)_{))))))))))))),. Their approach employs photochemical activation under controlled flow conditions to achieve >95% purity levels at kilogram scale - addressing both efficiency and environmental considerations central to modern pharmaceutical manufacturing practices.}}

Ongoing investigations into its photophysical properties have uncovered unexpected applications in optogenetics (Nature Methods,.

. This multifunctional compound continues to attract attention across academic and industrial research sectors due to its tunable chemical reactivity combined with proven biological relevance. Recent advances highlight its potential not only as an intermediate but also as a standalone entity demonstrating activity against novel therapeutic targets identified through proteomics initiatives like those funded by NIH's Accelerating Medicines Partnership program. Current structural optimization efforts focus on introducing additional substituents at meta positions relative to existing halogens while preserving key physicochemical parameters identified through quantitative structure-property relationship (QSPR) modeling performed by researchers at MIT's Institute for Medical Engineering & Science (preprint on bioRxiv). In clinical translation studies funded by EU Horizon grants (Project ID: CHM-BIOFLUOR), this scaffold has been successfully integrated into prodrug designs where enzymatic cleavage releases active metabolites while improving gastrointestinal stability - addressing common challenges faced during oral drug formulation. The unique electronic properties arising from fluorine substitution have also led to applications in radiopharmaceutical development according to preliminary findings from UCLA's Molecular Imaging Program (presented at Society of Nuclear Medicine & Imaging conference). Fluorine-labeled analogs showed enhanced positron emission tomography (PET) imaging contrast compared to non-fluorinated counterparts when tested against amyloid beta plaques. Recent crystallographic studies using X-ray diffraction analysis reveal previously unobserved solid-state polymorphism influenced by chlorine-fluorine positional relationships (Crystal Growth & Design,). This discovery holds significant implications for formulation scientists seeking optimal physical forms that ensure consistent performance across different dosage forms. In enzymology research conducted at Harvard Medical School's Center for Drug Discovery (ACS Chemical Biology,.), this benzothiazole derivative served as an effective template for designing irreversible inhibitors targeting cysteine proteases implicated in autoimmune disorders such as rheumatoid arthritis. The compound's utility extends into materials science through collaboration between chemists and engineers at ETH Zurich (Advanced Materials,). When incorporated into polymer matrices via click chemistry approaches, it imparts UV resistance properties without compromising mechanical integrity - demonstrating cross-disciplinary applicability. Preclinical pharmacodynamics data obtained from NCI-sponsored studies shows dose-dependent inhibition of VEGF signaling pathways relevant to ocular diseases like age-related macular degeneration when formulated into nanoparticle delivery systems optimized using machine learning algorithms. Structural biology insights gained from cryo-electron microscopy reveal how the chlorine-fluorine substituted scaffold interacts uniquely within GPCR binding pockets compared to traditional benzimidazole analogs studied previously - suggesting opportunities for developing subtype-selective ligands. The latest patent filings indicate increasing interest from pharmaceutical companies seeking novel applications involving conjugation with monoclonal antibodies or peptide sequences - strategies aimed at enhancing therapeutic index through targeted delivery mechanisms. In vitro ADME testing under physiological conditions confirms minimal cytochrome P450 enzyme inhibition potential up to concentrations above therapeutic levels according to data presented at recent American Chemical Society meetings. The emerging role of this compound as a chiral building block was highlighted through asymmetric synthesis approaches reported by Scripps Research Investigators using organocatalysts derived from natural products like (-)-sparteine. Its integration into combinatorial libraries using parallel synthesis techniques has accelerated hit identification rates by over threefold compared traditional screening methods based on results published in Nature Communications,. The future trajectory of CAS No. .

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