Topiroxostat
[CAS# 577778-58-6]

Identification

• Classification: API >> Other chemicals
• Name: Topiroxostat
• Synonyms: 5-(2-Cyano-4-pyridyl)-3-(4-pyridyl)-1,2,4-triazole; FYX 051
• Molecular Formula: C₁₃H₈N₆
• Molecular Weight: 248.24
• CAS Registry Number: 577778-58-6
• SMILES: C1=CN=CC=C1C2=NC(=NN2)C3=CC(=NC=C3)C#N

Properties

• Solubility: 10 mM (DMSO) (Expl.)
• Density: 1.45±0.1 g/cm³ (20 °C 760 Torr), Calc.^*
• Index of Refraction: 1.697, Calc.^*
• Boiling Point: 594.7±60.0 °C (760 mmHg), Calc.^*
• Flash Point: 175.3±18.1 °C, Calc.^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software V11.02 (©1994-2014 ACD/Labs)

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H315-H319-H335
• Safety Statements: P261-P305+P351+P338

Discovery and Applications

Topiroxostat is a novel pharmaceutical compound primarily used in the treatment of hyperuricemia and gout. It is classified as an xanthine oxidase inhibitor, which means it works by inhibiting the enzyme xanthine oxidase, a key enzyme involved in the production of uric acid. Elevated uric acid levels are a major contributor to the development of gout, a form of arthritis characterized by painful joint inflammation. By reducing the production of uric acid, Topiroxostat helps to manage and prevent gout attacks.

The discovery of Topiroxostat emerged from the ongoing search for effective treatments for gout and hyperuricemia. Gout is a prevalent condition, and the development of new therapies to control uric acid levels has been a significant focus in medical research. Traditional treatments, such as allopurinol, have been widely used, but they are not always effective in all patients and can cause side effects. Topiroxostat was developed as an alternative with a different chemical structure and mechanism of action, aiming to improve efficacy and reduce adverse effects in patients who are unable to tolerate other medications.

Synthetically, Topiroxostat is prepared through a series of chemical reactions that build upon the basic scaffold of xanthine oxidase inhibitors. The synthesis involves the selective functionalization of a benzene ring with specific groups to enhance the compound's potency and selectivity for xanthine oxidase. Its design ensures that it has a strong affinity for the enzyme, which allows it to efficiently lower uric acid levels in the bloodstream. Topiroxostat is administered orally, and it has been shown to have a favorable pharmacokinetic profile, providing sustained effects with minimal dosage requirements.

In clinical applications, Topiroxostat is primarily used to treat patients with chronic gout and hyperuricemia. By lowering serum uric acid levels, it reduces the frequency and severity of gout attacks and prevents the formation of urate crystals in joints, which can lead to painful inflammation. It has been particularly beneficial for patients who have not responded well to other treatments like allopurinol or those who experience side effects. The drug has been well received in markets such as Japan, where it has been approved for clinical use. Its success in clinical trials, demonstrating both efficacy and safety, has also led to interest in its potential use for other conditions associated with elevated uric acid levels, such as kidney disease and cardiovascular diseases.

Topiroxostat is a promising addition to the armamentarium of drugs available for managing gout and hyperuricemia. Its discovery and development have provided an important treatment option for patients who suffer from these conditions, with the added benefit of potentially fewer side effects compared to older medications. As research continues, further insights into its full range of therapeutic applications may expand its use in other diseases linked to uric acid metabolism.

References

2024. Topiroxostat-A Safer Uricostatic Drug with Enhanced Renal Protection: A Narrative Review. The Journal of the Association of Physicians of India.
DOI: 39563126

2024. Topiroxostat improves glomerulosclerosis in type 2 diabetic Nagoya Shibata Yasuda mice with early diabetic kidney disease. European Journal of Pharmacology.
DOI: 391548

2024. A comprehensive review of synthetic and semisynthetic xanthine oxidase inhibitors / identification of potential leads based on in-silico computed ADME characteristics. Molecular Diversity.
DOI: 39164505