Design, synthesis and biological evaluation of novel indole-3-carboxylic acid derivatives with antihypertensive activity

Abstract

Molecular design, synthesis, in vitro and in vivo studies of novel derivatives of indole-3-carboxylic acid new series of angiotensin II receptor 1 antagonists is presented. Radioligand binding studies using [¹²⁵I]-angiotensin II displayed that new derivatives of indole-3-carboxylic acid have a high nanomolar affinity for the angiotensin II receptor (AT₁ subtype) on a par with the known pharmaceuticals such as losartan. Biological studies of synthesized compounds in spontaneously hypertensive rats have demonstrated that compounds can lower blood pressure when administered orally. Maximum the decrease in blood pressure was 48 mm Hg with oral administration of 10 mg/kg and antihypertensive effect was observed for 24 h, which is superior to losartan.

Keywords: Angiotensin II receptor 1 antagonist; Antihypertension drug; Hypertension; Indole-3-carboxylic acid.