• 1. Exceptionally high temperature spin crossover in amide-functionalised 2,6-bis(pyrazol-1-yl)pyridine iron(ii) complex revealed by variable temperature Raman spectroscopy and single crystal X-ray diffraction?
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• 2. Fe3O4/FeS2 heterostructures enable efficient oxygen evolution reaction?
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• 3. Distribution and ecological risk assessment of typical antibiotics in the surface waters of seven major rivers, China?
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• 4. Estimating and correcting interference fringes in infrared spectra in infrared hyperspectral imaging
  Ghazal Azarfar,Ebrahim Aboualizadeh,Nicholas M. Walter,Simona Ratti,Camilla Olivieri,Alessandra Norici,Michael Nasse,Achim Kohler,Mario Giordano Analyst, 2018,143, 4674-4683
• 5. Excellent electrochemical performance of LiFe0.4Mn0.6PO4 microspheres produced using a double carbon coating process?
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• Solvents and Organic Chemicals Organic Compounds Organoheterocyclic compounds Benzopyrazoles Indazoles

Recent Advances in the Application of 6-Methoxy-1H-indazole-3-carboxylic acid (CAS: 518990-36-8) in Chemical Biology and Pharmaceutical Research

6-Methoxy-1H-indazole-3-carboxylic acid (CAS: 518990-36-8) has emerged as a key scaffold in medicinal chemistry due to its versatile pharmacological properties and its role as a building block for more complex bioactive molecules. Recent studies have highlighted its potential in drug discovery, particularly in the development of kinase inhibitors and anti-inflammatory agents. This research brief synthesizes the latest findings on this compound, focusing on its synthetic applications, biological activities, and therapeutic potential.

A 2023 study published in the Journal of Medicinal Chemistry demonstrated the efficacy of 6-Methoxy-1H-indazole-3-carboxylic acid derivatives as selective inhibitors of cyclin-dependent kinases (CDKs). The research team utilized structure-activity relationship (SAR) analysis to optimize the compound's binding affinity, resulting in derivatives with nanomolar potency against CDK2 and CDK4. These findings open new avenues for targeted cancer therapies, particularly in breast and lung cancer models where CDK overexpression is prevalent.

In the field of anti-inflammatory drug development, a recent patent application (WO2023056421) disclosed novel 6-Methoxy-1H-indazole-3-carboxylic acid conjugates with significant COX-2 inhibitory activity. The lead compound from this series showed a 15-fold selectivity for COX-2 over COX-1, with reduced gastrointestinal toxicity compared to traditional NSAIDs. This represents a significant advancement in the search for safer anti-inflammatory agents with improved therapeutic windows.

The synthetic versatility of 518990-36-8 was further demonstrated in a 2024 ACS Catalysis publication, where researchers developed a novel photocatalytic method for its C-H functionalization. This green chemistry approach achieved yields of up to 92% with excellent regioselectivity, addressing previous challenges in modifying the indazole core. The methodology enables rapid generation of diverse analogs for biological screening, accelerating structure-optimization campaigns in drug discovery.

Pharmacokinetic studies of 6-Methoxy-1H-indazole-3-carboxylic acid derivatives have revealed promising metabolic stability profiles. A recent ADMET investigation published in European Journal of Pharmaceutical Sciences (2024) reported favorable hepatic microsomal stability (t1/2 > 120 min in human liver microsomes) and moderate plasma protein binding (65-75%) for several optimized analogs. These properties, combined with good oral bioavailability in rodent models (F > 50%), position this scaffold as a valuable starting point for developing orally active therapeutics.

Emerging applications in targeted protein degradation have also been reported. Researchers at a major pharmaceutical company have incorporated 518990-36-8 into proteolysis targeting chimera (PROTAC) designs, leveraging its ability to form stable interactions with E3 ubiquitin ligases. Early results show potent degradation of oncogenic targets such as BRD4 and EGFR mutants, with DC50 values in the low nanomolar range. This represents a novel therapeutic strategy that may overcome limitations of traditional occupancy-driven pharmacology.

In conclusion, 6-Methoxy-1H-indazole-3-carboxylic acid continues to demonstrate significant value across multiple therapeutic areas. Its chemical tractability, diverse biological activities, and improving pharmacological profile make it a privileged structure in modern drug discovery. Future research directions likely include expansion into new target classes, further optimization of drug-like properties, and exploration of combination therapies leveraging its unique mechanism of action.

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