Synthesis and pharmacological evaluation of a novel AT₁ angiotensin II receptor antagonist with anti-hypertension and anti-tumor effects

Abstract

A new compound 2-(4-((2-butyl-5-nitro-1H-benzo[d]imidazol-1-yl)methyl)-1H-indol-1-yl) benzamide (1) was designed, synthesized and evaluated as a novel AT₁ receptor antagonist. Compound 1 displayed high affinity to AT₁ receptor with an IC₅₀ value of 1.65 ± 0.2 nM in radio-ligand binding assays. It had an efficient and long-lasting effect in reducing blood pressure which could last for more than 12 h at the dose of 10 mg/kg in spontaneously hypertensive rats. Acute toxicity tests suggested that compound 1 was safe with the LD₅₀ value of 2519.81 mg/kg. Besides, in vitro and in vivo tests suggested its anti-proliferative and anti-tumor activities, respectively. So compound 1 could be considered as a novel anti-hypertension, anti-tumor candidate and deserved further investigation.

• Angiotensin II receptor antagonist
• anti-hypertension
• anti-tumor
• hypertension
• tumor

Declaration of interest

This work was supported by National Natural Science Foundation of China (No. 21372042, 21402236, 81101298, 81301878), Science and Technology Commission of Shanghai Municipality (No. 13431900700, 14431906200, 13430722300, 14140903500, 13ZR1441000, 13ZR1440900), International Cooperation Foundation of China (6–11). The authors declare no conflict of interests.