Synthesis and biological evaluation of novel potent angiotensin II receptor antagonists with anti-hypertension effect

被引：16

作者：

Nie, Yong-yan ^{[1
]}

Da, Ya-jing ^{[1
]}

Zheng, Hao ^{[1
]}

Yang, Xiao-xia ^{[1
]}

Jia, Lin ^{[1
]}

Wen, Cai-hong ^{[1
]}

Liang, Li-sha ^{[1
]}

Tian, Juan ^{[1
]}

Chen, Zhi-long ^{[1
]}

机构：

[1] Donghua Univ, Dept Pharmaceut Sci & Technol, Coll Chem & Biol, Shanghai 201600, Peoples R China

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2012年 / 20卷 / 08期

关键词：

Angiotensin II receptor antagonists; Hypertension; Synthesis; Acute toxicity; PHARMACOLOGY;

D O I：

10.1016/j.bmc.2012.02.003

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 IC50 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 LD50 value of compound 1b was 2316.8 mg/kg which was lower than valsartan (LD50 = 307.50 mg/kg) but higher than losartan (LD50 = 2248 mg/kg). So they could be considered as novel anti-hypertension candidates and deserved for further investigation. (C) 2012 Elsevier Ltd. All rights reserved.

引用

页码：2747 / 2761

页数：15

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