Lesinurad
[CAS# 878672-00-5]

Identification

• Classification: API >> Other chemicals
• Name: Lesinurad
• Synonyms: 2-[[5-Bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1,2,4-triazol-3-yl]thio]acetic acid; RDEA 594
• Molecular Formula: C₁₇H₁₄BrN₃O₂S
• Molecular Weight: 404.28
• CAS Registry Number: 878672-00-5
• EC Number: 689-245-8
• SMILES: C1CC1C2=CC=C(C3=CC=CC=C23)N4C(=NN=C4Br)SCC(=O)O

Properties

• Solubility: Insoluble (1.5E^-4 g/L) (25 °C), Calc.^*, 29 mg/mL (DMSO) (Expl.)
• Density: 1.72±0.1 g/cm³ (20 °C 760 Torr), Calc.^*
• Index of Refraction: 1.776, Calc.^*
• Boiling Point: 643.7±65.0 °C (760 mmHg), Calc.^*
• Flash Point: 343.1±34.3 °C, Calc.^*

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

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H302
• Safety Statements: P264-P270-P301+P317-P330-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Acute toxicity	Acute Tox.	4	H302

Discovery and Applications

Lesinurad is a novel pharmaceutical compound primarily used in the treatment of gout, a condition characterized by elevated levels of uric acid in the blood, leading to the formation of painful crystals in the joints. Lesinurad belongs to a class of drugs known as uricosuric agents, which work by increasing the excretion of uric acid through the kidneys. The development of Lesinurad aimed to address the limitations of existing treatments for gout by providing a more effective option for patients who have not responded adequately to other therapies.

The discovery of Lesinurad was driven by the need for better management of hyperuricemia, particularly in patients who had inadequate responses to xanthine oxidase inhibitors like allopurinol and febuxostat. These medications work by reducing the production of uric acid but are not always sufficient for all patients. Lesinurad, by contrast, works by inhibiting the reabsorption of uric acid in the kidneys, thereby promoting its elimination from the body. Specifically, Lesinurad targets the URAT1 (uric acid transporter 1) protein, which is responsible for the reabsorption of uric acid back into the bloodstream. By inhibiting this protein, Lesinurad increases the urinary excretion of uric acid, thus reducing blood uric acid levels.

Lesinurad is typically prescribed in combination with a xanthine oxidase inhibitor for patients with gout who have not achieved sufficient uric acid control with monotherapy. The combination of Lesinurad and a xanthine oxidase inhibitor can provide a more comprehensive approach to managing gout by addressing both the production and elimination of uric acid. This combination therapy is particularly beneficial for patients who experience frequent gout flares or who have a history of complications related to high uric acid levels, such as kidney stones.

The approval of Lesinurad by regulatory agencies, such as the U.S. Food and Drug Administration (FDA), marked an important step forward in the treatment of gout. Clinical studies demonstrated that Lesinurad, when used alongside a xanthine oxidase inhibitor, effectively lowered serum uric acid levels and reduced the frequency of gout flares in patients with uncontrolled hyperuricemia. These results established Lesinurad as a valuable therapeutic option for those suffering from chronic gout.

In addition to its role in treating gout, Lesinurad’s unique mechanism of action has spurred interest in exploring its potential applications in other conditions associated with elevated uric acid levels. There is ongoing research into whether Lesinurad could be used to treat conditions such as kidney disease, where high uric acid levels may contribute to kidney damage. Additionally, Lesinurad has shown promise in reducing the risk of cardiovascular events in patients with gout, as high uric acid levels are linked to an increased risk of heart disease.

In conclusion, Lesinurad represents a significant advancement in the management of gout, offering an effective option for patients who do not respond adequately to conventional treatments. Its ability to increase uric acid excretion through the kidneys provides a complementary approach to existing therapies, making it an important tool in the fight against gout and related conditions.

References

2023. Different spectrophotometric methods for simultaneous determination of lesinurad and allopurinol in the new FDA approved pharmaceutical preparation; additional greenness evaluation. Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy.
DOI: 10.1016/j.saa.2022.121868

2023. Emerging Urate-Lowering Drugs and Pharmacologic Treatment Strategies for Gout: A Narrative Review. Drugs, 83(14).
DOI: 10.1007/s40265-023-01944-y

2024. Recent application of green analytical chemistry: eco-friendly approaches for pharmaceutical analysis. Future Journal of Pharmaceutical Sciences, 10(1).
DOI: 10.1186/s43094-024-00658-6