Related Experiment Video
Updated: May 28, 2026

Amide Coupling Reaction for the Synthesis of Bispyridine-based Ligands and Their Complexation to Platinum as Dinuclear Anticancer Agents
Published on: May 28, 2014
Pyridoimidazolyl Sulfonamide Compound 2: A Superior Dual-Acting Drug Candidate with Potent URAT1 Inhibition and
Xiaoyu Shi1, Cheng Shi2, Mingyu Yang1
1Department of Medicinal Chemistry, State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, Jinan, Shandong 250012, P.R. China.
Abstract:
The management of hyperuricemia and gout remains constrained by the narrow therapeutic index of current drugs. To improve the druggability of our previously identified URAT1 inhibitor T7, we replaced its carboxylic acid with a sulfonamide group. A total of 40 novel derivatives were synthesized, among which 23 derivatives exhibited robust in vivo serum uric acid-lowering activity. Lead compound 2 (bearing a p-bromobenzenesulfonamide) exhibited potent URAT1 inhibition (IC50 = 0.19 μM) and significantly lowered serum uric acid in hyperuricemic mice (96.8% reduction) and rats (91.9% reduction). Notably, compound 2 also inhibited IL-1β activity (IC50 = 3.39 μM), which may enhance its therapeutic potential in gout by targeting disease-associated inflammation. Compound 2 demonstrated favorable pharmacokinetics (half-life: 6.3 h, oral bioavailability: 20.1%) and high safety (MTD > 1000 mg/kg). These results establish compound 2 as a promising dual-acting candidate for gout therapy.
Related Concept Videos
Drugs for Treatment of Ulcerative Colitis in IBD
Antihypertensive Drugs: Thiazide-Class Diuretics
Acid Suppressive Drugs for Peptic Ulcer Disease: Histamine H2-Receptor Antagonists
Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase
Renal Drug Excretion: Tubular Secretion
Treatment for Pulmonary Arterial Hypertension: Prostacyclin Receptor Agonists
These agonists bind to the IPR receptor situated on the plasma membrane of the pulmonary artery smooth muscle cells. This binding triggers a cascade of reactions known as the GS-AC-cAMP-PKA pathway. This pathway results in the relaxation of smooth muscle...