Synthesis of the first sulfur-35-labeled hERG radioligand

• Published in: Bioorganic & medicinal chemistry letters Vol. 16; no. 6; pp. 1692 - 1695
• Main Authors: Raab, Conrad E., Butcher, John W., Connolly, Thomas M., Karczewski, Jerzy, Yu, Nathan X., Staskiewicz, Steven J., Liverton, Nigel, Dean, Dennis C., Melillo, David G.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 15.03.2006; Elsevier
• Subjects: Benzopyrans - chemistry; Benzopyrans - pharmacology; Biological and medical sciences; Contrast media. Radiopharmaceuticals; Ether-A-Go-Go Potassium Channels - antagonists & inhibitors; Ether-A-Go-Go Potassium Channels - metabolism; hERG; Humans; Medical sciences; Pharmacology. Drug treatments; Piperidines - chemistry; Piperidines - pharmacology; Potassium Channel Blockers - chemical synthesis; Potassium Channel Blockers - pharmacology; Radioligand; Radioligand Assay; Radiopharmaceuticals - chemical synthesis; Radiopharmaceuticals - pharmacology; S-35; Sulfur Radioisotopes - chemistry; Synthesis; hERG; S-35; Radioligand; Synthesis; Nitrile; Sulfonamide; Arrhythmia; Radiolabelling; Sulfur 35; Ligand; Cardiovascular disease; Ionic channel; Tricyclic compound; Potassium Ions; Diastereoselectivity; Spiran; Heart disease; Affinity; Aromatic compound; Secondary alcohol; Chemical synthesis; Oxygen nitrogen heterocycle; Sulfur Isotopes
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2005.12.021

The synthesis of hERG radioligand [35S]MK-0499 for use in an HTS assay for IKr activity is reported The synthesis of the first high specific activity S-35-labeled hERG radioligand, [35S]MK-0499, for use in HTS assays of drug candidates for hERG interaction is described. The radioligand is prepared by [35S]sulfonylation of a high diastereomeric excess (de) aniline precursor prepared from unlabeled MK-0499.