Urea transporter and its specific and nonspecific inhibitors: State of the art and pharmacological perspective

Abstract

Hypertension is a major concern for a wide array of patients. The traditional drugs are commonly referred as 'water pills' and these molecules have been successful in alleviating hypertension. However, this comes at the high expense of precious electrolytes in our body. To dissipate this major adverse effect, the urea transporter inhibitors play especially important roles in maintaining the fluid balance by maintaining the concentration of urea in the inner medullary collecting duct. The purpose of this communication is to provide insights into the structural feature of these target proteins and inhibition of both urea transporter types A (UT-A) and B (UT-B) selectively and non-selectively with a special focus on the UT-A inhibitors as they are the primary target for diuresis. It was observed that a wide class of drugs such as thiourea analogues, 2,7-disubstituted fluorenones can inhibit both the protein non-selectively whereas 8-hydroxyquinoline, aminothiazolone, 1,3,5-triazine, triazolothienopyrimidine, thienoquinoline, arylthiazole, γ-sultambenzosulfonamide and 1,2,4-triazoloquinoxaline classes of compounds inhibit UT-A. The goal of this study is to highlight the important aspects that may be useful to understanding the perspectives of urea transporter inhibitors in rational drug discovery.

Keywords: Diuretics; Medicinal chemistry; SAR; UT inhibitors; UT-A; Urea transporter.