•New AT1 blockers with a chiral center were synthesized.•Eight compounds were potent in the AT1 antagonism in vitro.•One compound was of excellent efficacy in antihypertension and low toxicity.•The best molecule showed strong interactions with the AT1 model in docking study.Novel angiotensin II receptor type 1 (AT1) blockers bearing 6-substituted carbamoyl benzimidazoles with a chiral center were designed and synthesized as the first step to develop new antihypertensive agents and understand their pharmacodynamic and pharmacokinetic properties. The newly synthesized compounds were tested for their potential ability to displace [125I] Sar1 Ile8-Ang II, which was specifically bound to human AT1 receptor. Radioligand binding assays revealed nanomolar affinity in several compounds under study. The IC50 values of nine ligands were higher than those of Losartan. The screening of decreased blood pressure in spontaneous hypertensive rats displayed that compound 8S (IC50 = 5.0 nM) was equipotent with Losartan, whereas compounds 13R (IC50 = 7.3 nM), 14R (IC50 = 6.3 nM), and 14S (IC50 = 3.5 nM) were slightly ahead of Losartan, and the most significant activity was demonstrated by compound 8R (IC50 = 1.1 nM). Candidate 8R was identified for its excellent efficacy in antihypertension and fairly low toxicity based on plasma analyses, toxicology studies, and chronic oral tests. Finally, compound 8R exhibited strong and multiple interactions with target active sites of the theoretical AT1 receptor model in docking study.

Newly developed ferrocene–oxazoline–phosphine ligands containing quaternary ammonium ionic groups exhibited excellent catalytic performance for the ruthenium-catalyzed hydrogenation of aromatic ketonic substrates to give chiral secondary alcohols with high levels of conversions and enantioselectivities. Simple manipulation process, water tolerance, high activity and good recyclable property make this catalysis practical and appealing.