Referenced in: none

Automatically associated channels: Kv11.1

Title: Quinazolin-4-piperidin-4-methyl sulfamide PC-1 inhibitors: alleviating hERG interactions through structure based design.

Authors: Snahel D Patel, Wendy M Habeski, Alan C Cheng, Elisa de la Cruz, Christine Loh, Natasha M Kablaoui

Journal, date & volume: Bioorg. Med. Chem. Lett., 2009 Jun 15 , 19, 3339-43

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/19435660

Abstract
PC-1 (NPP-1) inhibitors may be useful as therapeutics for the treatment of CDDP (calcium pyrophosphate dehydrate) deposition disease and osteoarthritis. We have identified a series of potent quinazolin-4-piperidin-4-ethyl sulfamide PC-1 inhibitors. The series, however, suffers from high affinity binding to hERG potassium channels, which can cause drug-induced QT prolongation. We used a hERG homology model to identify potential key interactions between our compounds and hERG, and the information gained was used to design and prepare a series of quinazolin-4-piperidin-4-methyl sulfamides that retain PC-1 activity but lack binding affinity for hERG.