Synthesis of the first sulfur-35-labeled hERG radioligand

Conrad E Raab; John W Butcher; Thomas M Connolly; Jerzy Karczewski; Nathan X Yu; Steven J Staskiewicz; Nigel Liverton; Dennis C Dean; David G Melillo

doi:10.1016/j.bmcl.2005.12.021

Synthesis of the first sulfur-35-labeled hERG radioligand

Bioorg Med Chem Lett. 2006 Mar 15;16(6):1692-5. doi: 10.1016/j.bmcl.2005.12.021. Epub 2006 Jan 11.

Authors

Conrad E Raab¹, John W Butcher, Thomas M Connolly, Jerzy Karczewski, Nathan X Yu, Steven J Staskiewicz, Nigel Liverton, Dennis C Dean, David G Melillo

Affiliation

¹ Department of Drug Metabolism, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065, USA. conrad_raab@merck.com

PMID: 16377185
DOI: 10.1016/j.bmcl.2005.12.021

Abstract

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

MeSH terms

Benzopyrans / chemistry*
Benzopyrans / pharmacology*
Ether-A-Go-Go Potassium Channels / antagonists & inhibitors*
Ether-A-Go-Go Potassium Channels / metabolism
Humans
Piperidines / chemistry*
Piperidines / pharmacology*
Potassium Channel Blockers / chemical synthesis*
Potassium Channel Blockers / pharmacology
Radioligand Assay
Radiopharmaceuticals / chemical synthesis*
Radiopharmaceuticals / pharmacology
Sulfur Radioisotopes / chemistry

Substances

Benzopyrans
Ether-A-Go-Go Potassium Channels
Piperidines
Potassium Channel Blockers
Radiopharmaceuticals
Sulfur Radioisotopes
L 706000