title: Synthesis and biological evaluation of novel potent angiotensin II receptor antagonists with anti-hypertension effect.
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.
authors.affiliation: Department of Pharmaceutical Science and Technology, College of Chemistry and Biology, Donghua University, Shanghai 201600, China.
authors.forename: Yong-yan
authors.initials: YY
authors.lastname: Nie
authors.forename: Ya-jing
authors.initials: YJ
authors.lastname: Da
authors.forename: Hao
authors.initials: H
authors.lastname: Zheng
authors.forename: Xiao-xia
authors.initials: XX
authors.lastname: Yang
authors.forename: Lin
authors.initials: L
authors.lastname: Jia
authors.forename: Cai-hong
authors.initials: CH
authors.lastname: Wen
authors.forename: Li-sha
authors.initials: LS
authors.lastname: Liang
authors.forename: Juan
authors.initials: J
authors.lastname: Tian
authors.forename: Zhi-long
authors.initials: ZL
authors.lastname: Chen
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D008968:Molecular Conformation; D015394:Molecular Structure; D051381:Rats; D011918:Rats, Inbred SHR
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents