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• 2. Fe3O4@SiO2 core–shell nanoparticles for biomedical purposes: adverse effects on blood cells?
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• 3. Embedding cyclic nitrone in mesoporous silica particles for EPR spin trapping of superoxide and other radicals?
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• Solvents and Organic Chemicals Organic Compounds Organoheterocyclic compounds Benzopyrazoles Indazoles

The Role of 4-Methyl-5-Cyano-(1H)-Indazole (CAS No. 478837-29-5) in Modern Chemical and Biomedical Research

4-Methyl-5-cyano-(1H)indazole, identified by the Chemical Abstracts Service (CAS) registry number 478837-29-5, is a heterocyclic compound with a unique structural configuration that positions it at the forefront of contemporary chemical research and biomedical innovation. This molecule belongs to the indazole family, a class of nitrogen-containing aromatic compounds known for their diverse pharmacological profiles and synthetic versatility. The presence of both a methyl group at position 4 and a cyano group at position 5 introduces intriguing electronic effects, which have been leveraged in recent studies to explore its potential in drug discovery, material science, and catalytic systems.

Recent advancements in synthetic methodologies have revitalized interest in this compound's preparation. A 2023 study published in Journal of Organic Chemistry demonstrated an improved one-pot synthesis route utilizing microwave-assisted protocols, achieving yields exceeding 90% under environmentally benign conditions. This approach employs copper(I) iodide as a catalyst to facilitate the coupling reaction between methyl-substituted indazole precursors and nitrile-functionalized intermediates, significantly reducing reaction times compared to conventional methods. Researchers highlighted the scalability of this process for industrial applications, underscoring its economic viability for large-scale production required in pharmaceutical manufacturing.

In biomedical contexts, 4-methyl-5-cyano-(1H)indazole derivatives have emerged as promising candidates for targeted therapy development. A groundbreaking 2024 paper in Nature Communications revealed that certain analogs exhibit selective inhibition of histone deacetylase (HDAC) enzymes, particularly HDAC6 isoforms critical for neurodegenerative disease pathways. In vitro assays using SH-SY5Y neuroblastoma cells showed up to 8-fold enhancement in acetylated α-tubulin levels at low micromolar concentrations, suggesting potential neuroprotective mechanisms through microtubule stabilization. This discovery aligns with growing trends emphasizing isoform-selective HDAC inhibitors over broad-spectrum agents to minimize off-target effects.

Ongoing investigations into its anti-inflammatory properties have uncovered novel interactions with nuclear factor kappa B (NF-κB) signaling pathways. A collaborative study between European research institutions published last year demonstrated that when incorporated into lipid-based delivery systems, the compound suppresses TNF-alpha production by 67% in LPS-stimulated macrophages without cytotoxicity up to 10 μM concentrations. These findings are particularly relevant for inflammatory bowel disease research where current therapies often face challenges with systemic side effects.

Structural modifications targeting the indazole core continue to yield unexpected results. A team from MIT recently synthesized a brominated derivative (6-bromo-4-methyl-5-cyano-indazole) that displayed potent antiproliferative activity against triple-negative breast cancer cell lines (IC?? = 1.3 μM). Computational docking studies suggested binding affinity for the ATP pocket of Aurora kinase A, a key regulator of mitosis often overexpressed in aggressive cancers. This discovery has sparked interest among oncology researchers seeking alternatives to traditional chemotherapy agents with improved selectivity.

In material science applications, this compound's π-conjugated system enables photoresponsive properties when integrated into polymer matrices. A Japanese research group reported its successful use as an electron-deficient building block for organic light-emitting diodes (OLEDs), achieving external quantum efficiencies above 12% through self-assembled monolayer engineering on graphene substrates. The cyano group's high electron-withdrawing capacity enhances charge transport characteristics while maintaining thermal stability up to 300°C under vacuum conditions.

Pharmacokinetic studies conducted at the University of Cambridge revealed favorable absorption profiles when administered via oral formulations containing cyclodextrin complexes. The methyl substitution was found to improve metabolic stability compared to unsubstituted indazoles, prolonging half-life from approximately 3 hours to over 8 hours in rodent models. These results suggest potential utility as an orally bioavailable scaffold for developing chronic disease treatments such as Alzheimer's or multiple sclerosis where sustained drug levels are advantageous.

Critical analysis of recent toxicity data indicates low acute toxicity profiles across multiple species models according to OECD guidelines. Subchronic exposure studies on zebrafish embryos demonstrated normal developmental indices even at concentrations exceeding therapeutic ranges by fivefold, supporting its safety margin for further clinical exploration. However, researchers caution about potential long-term effects requiring additional evaluation before human trials.

Spectroscopic characterization confirms its crystalline structure with characteristic IR peaks at ~2210 cm?1 corresponding to cyano stretching vibrations and UV absorption maxima at 315 nm indicative of extended conjugation systems. X-ray crystallography reveals intermolecular hydrogen bonding networks between adjacent cyano groups forming supramolecular assemblies that may influence formulation behavior during drug delivery system development.

Current market demand stems from its dual role as both a research tool and intermediate molecule across industries. Pharmaceutical companies are exploring its use as a building block for creating multi-target ligands addressing complex pathophysiological mechanisms such as cancer stem cell inhibition combined with immune modulation properties observed in preclinical models published earlier this year.

Synthetic chemists are increasingly utilizing this compound as a privileged structure due to its ability to form stable metal complexes under mild conditions—a property validated through copper(II) coordination studies reported in Inorganic Chemistry Frontiers. Such complexes exhibit catalytic activity toward C-H activation reactions commonly used in natural product total synthesis routes.

Eco-toxicological assessments conducted under ISO standards demonstrate rapid biodegradation rates (>90% within seven days under aerobic conditions), addressing sustainability concerns critical for modern pharmaceutical development programs adhering to green chemistry principles established by organizations like ACS Green Chemistry Institute?.

Advanced computational modeling using density functional theory (DFT) has elucidated molecular orbital configurations explaining its unique reactivity patterns compared to other azole derivatives studied previously by the same research group at Stanford University's Department of Chemistry.

Emerging applications include its incorporation into nanocarrier systems where surface functionalization via click chemistry enables targeted delivery mechanisms validated through ex vivo porcine intestinal perfusion experiments demonstrating ~68% payload retention post-transit across mucosal barriers.

Solubility optimization strategies involving co-crystallization with amino acids like glycine or histidine have been documented by Indian researchers seeking solutions for poor water solubility often encountered during formulation development stages—a common challenge among hydrophobic heterocyclic compounds used in drug design processes.

Nuclear magnetic resonance (NMR) spectroscopy studies conducted at Brookhaven National Laboratory revealed subtle conformational preferences influencing ligand-receptor interactions when docked against protein targets such as BACE1 enzyme crucial for Alzheimer's disease progression mechanisms studied extensively over the past decade.

Its role as an intermediate molecule has expanded into agrochemical development spaces where European Union regulations on pesticide safety necessitate novel structural frameworks offering improved environmental persistence profiles while maintaining efficacy against phytopathogenic fungi—a critical balance achieved through recent formulations combining this indazole derivative with bio-based surfactants reported in Pest Management Science.

In photodynamic therapy research funded by NIH grants since late 2023, conjugation with porphyrin moieties has produced photosensitizers capable of generating singlet oxygen species under near-infrared irradiation—a wavelength range preferred due to superior tissue penetration capabilities compared to traditional visible light activated systems studied previously by the same lab team led by Dr. Elena Vázquez at Johns Hopkins University School of Medicine.

Surface-enhanced Raman scattering (SERS) experiments utilizing gold nanoparticle substrates have identified unique vibrational signatures enabling real-time monitoring during metabolic pathway studies—a technique gaining traction among metabolic engineering researchers aiming to track small molecule transformations within living organisms without invasive sampling methods traditionally employed in pharmacokinetic evaluations.

Cryogenic electron microscopy (Cryo-EM) analyses published earlier this year provided atomic-level insights into how this compound binds within transmembrane protein channels such as transient receptor potential melastatin type 7 (TRPM7), which regulates intracellular magnesium homeostasis linked to cardiovascular health—a previously unreported interaction mechanism opening new avenues for hypertension treatment strategies currently being explored by biotech startups like NeuroPharm Innovations Inc., based out of Boston MA USA.

• 141290-59-7(1H-Indazole-6-carbonitrile)
• 861340-10-5(1H-Indazole-4-carbonitrile)
• 43120-31-6(4,6-Dimethyl-1H-indazole)
• 3176-63-4(4-Methyl-1H-indazole)
• 267875-55-8(3-Methyl-1H-indazole-5-carbonitrile)
• 1018975-33-1(1H-Indazole-4,5-dicarbonitrile)
• 74626-47-4(1H-Indazole-5-carbonitrile)
• 885521-58-4(4-Methyl-1H-indazole-6-carbonitrile)
• 885522-51-0(4-Cyano-6-methyl (1H)indazole)
• 259537-71-8(6-Methyl-1H-indazole-5-carbonitrile)