Hyperuricemia is characterized by higher than normal blood levels of uric acid, sustained over long periods of time, often due to enhanced uric acid production (e.g., 10-20%) and/or reduced renal excretion (e.g., 80-90%) of uric acid. Hyperuricemia may be caused by numerous factors, such as obesity/weight gain, excessive alcohol use, excessive dietary purine intake, and certain medications, including low-dose aspirin, diuretics, niacin, cyclosporine, some high blood pressure drugs, some cancer chemotherapeutics, immunosuppressive and cytotoxic agents, and so on. In certain instances, hyperuricemia may be asymptomatic, but it may be associated with the following conditions: gout, gouty arthritis, uric acid stones in the urinary tract (urolithiasis), deposits of uric acid in the soft tissue (tophi), deposits of uric acid in the kidneys (uric acid nephropathy), and impaired kidney function, possibly leading to chronic and acute renal failure. Defective uric acid processing may lead to elevated levels of uric acid in the blood causing recurring attacks of joint inflammation (arthritis), uric acid deposits in and around the joints, tophaceous gout, formation of tophi, decreased kidney function, and kidney stones. Approximately 3 to 5 million people in the United States suffer from attacks of gout. In certain instances, gout is one of the most common forms of arthritis, accounting for approximately 5% of all arthritis cases. In certain instances, kidney failure and urolithiasis occur in 10-18% of individuals with gout and are common sources of morbidity and mortality from the disease.
Lesinurad inhibits the uric acid transporter 1 (URAT1) protein, increasing uric acid excretion and thereby lowering serum uric acid (sUA), and is an investigational agent now in phase III clinical trial for treatment of gout. In top-line results from a Phase III study on gout patients who did not obtain benefits from treatment with allopurinol and febuxostat, lesinurad alone significantly reduced serum levels of uric acid.
Lesinurad is known by its chemical name as 2-((5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1,2,4-triazol-3-yl)thio)acetic acid, having the structure of Formula I:

Two crystalline forms of lesinurad have been reported. (WO2012092395) In addition, polymorphic, crystalline and mesophase forms of lesinurad sodium salt (formula II) have also been reported. (WO2011085009) However, due to unpredictable properties of different crystalline forms for a specific compound, new crystalline forms of lesinurad and its sodium salt, in particular their stable polymorphs with superior pharmacological properties, and convenient methods to prepare them remain a great need.
USPTO Backgrounds
USPTO Backgrounds