Synthesis and biological evaluation of novel potent angiotensin II receptor antagonists with anti-hypertension effect |
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Authors: | Nie Yong-yan Da Ya-jing Zheng Hao Yang Xiao-xia Jia Lin Wen Cai-hong Liang Li-sha Tian Juan Chen Zhi-long |
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Institution: | Department of Pharmaceutical Science and Technology, College of Chemistry and Biology, Donghua University, Shanghai 201600, China. |
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Abstract: | A series of novel angiotensin II type 1 receptor antagonists were prepared. Radioligand binding assay suggested that compounds 1b and 1c could be recognized by the AT(1) receptor with an IC(50) value of 1.6 ± 0.09 nM and 2.64 ± 0.7 nM, respectively. In vivo anti-hypertension experiments showed that compounds (1a, 1b, 1c, 1e) elicited a significant decrease in SBP and DBP of spontaneous hypertensive rats (SHRs). The antihypertensive effects maintained for 10 h, which indicated that these compounds had a favorable blood pressure-lowering effect. Acute toxicity testing suggested that the LD(50) value of compound 1b was 2316.8 mg/kg which was lower than valsartan (LD(50)=307.50 mg/kg) but higher than losartan (LD(50)=2248 mg/kg). So they could be considered as novel anti-hypertension candidates and deserved for further investigation. |
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