In an attempt to improve GIRK1/GIRK2 selectivity, Sharma et al generated a family of tetrazol-acetamides [39], based on a molecule from their first HTS [25]. These tetrazol-acetamides were shown to be GIRK1/GIRK2 activators in the thallium flux assay [39]. However, neither the selectivity nor the pharmacokinetic properties were significantly improved with this change of scaffold [39].
