Structural optimization of losartan as an approach to the design of new angiotensin II receptor antagonists

Abstract

Arterial hypertension (AH) remains one of the leading causes of mortality worldwide. Even with the availability of effective medications, a considerable proportion of patients fail to achieve target blood pressure levels, which highlights the need for developing new molecules with improved therapeutic profiles [1]. One of the widely used agents for the treatment of hypertension is losartan – the first non-peptide antagonist of the angiotensin II type 1 receptor (AT₁). Since losartan requires metabolic activation, resulting in variability of the pharmacological effect, and other sartans (valsartan, candesartan, telmisartan) have their own drawbacks – such as low solubility, excessive lipophilicity, or limited bioavailability – this creates a strong rationale for rational structural optimization