The therapeutic potential of targeting the Kir1.1 (renal outer medullary K(+)) channel.

K(ir)1.1 (renal outer medullary K+) channels are potassium channels expressed almost exclusively in the kidney andents the role of transporter play a role in the body's electrolyte and water balance. Potassium efflux through K(ir)1.1 complims and sodium channels that are the targets of known diuretics. Consequently, loss-of-function mutations in men and rodents are associated with salt wasting and low blood pressure. On this basis, K(ir)1.1 inhibitors may have value in the treatment of hypertension and heart failure. Efforts to develop small molecule K(ir)1.1 inhibitors produced MK-7145, which entered into clinical trials. The present manuscript describes the structure-activity relationships associated with this scaffold alongside other preclinical K(ir)1.1 blockers.