Design, synthesis, and pharmacological evaluation of 5-oxo-1,2,4-oxadiazole derivatives as AT1 antagonists with antihypertension activities

A series of new 5-oxo-1,2,4-oxadiazole derivatives with 1, 4-disubsituted or 1, 5-disubsituted indole group was designed, synthesized, and pharmacologically evaluated. These derivatives displayed high affinities to the AT 1 receptor at the same order of magnitude to losartan. The methyl ester with 1...

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Published in:Clinical and experimental hypertension (1993) 2016-07, Vol.38 (5), p.435-442
Main Authors: Zhu, Weibo, Bao, Xiaolu, Ren, He, Liao, Pingyong, Zhu, Wei, Yan, Yijia, Wang, Li, Chen, Zhilong
Format: Article
Language:English
Subjects:
5-oxo-1
acute toxicity
Administration, Oral
Angiotensin II Type 1 Receptor Blockers - chemical synthesis
Angiotensin II Type 1 Receptor Blockers - chemistry
Angiotensin II Type 1 Receptor Blockers - pharmacology
Animals
antagonists
Antihypertension
Antihypertensive Agents - chemical synthesis
Antihypertensive Agents - chemistry
Antihypertensive Agents - pharmacology
Benzimidazoles - chemical synthesis
Benzimidazoles - chemistry
Benzimidazoles - pharmacology
Biphenyl Compounds - chemical synthesis
Biphenyl Compounds - chemistry
Biphenyl Compounds - pharmacology
Female
Hypertension - drug therapy
Losartan - chemical synthesis
Losartan - chemistry
Losartan - pharmacology
Male
N-phenyl indole
oxadiazole
Oxadiazoles - chemical synthesis
Oxadiazoles - chemistry
Oxadiazoles - pharmacology
Rats, Inbred SHR
Tetrazoles - chemical synthesis
Tetrazoles - chemistry
Tetrazoles - pharmacology
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Summary:A series of new 5-oxo-1,2,4-oxadiazole derivatives with 1, 4-disubsituted or 1, 5-disubsituted indole group was designed, synthesized, and pharmacologically evaluated. These derivatives displayed high affinities to the AT 1 receptor at the same order of magnitude to losartan. The methyl ester with 1, 4-disubsituted indole group, 1 (5.01 ± 1.67 nM) showed high antihypertension activity on spontaneously hypertensive rats (SHRs). Its maximal response lowered 30 mmHg of mean blood pressure (MBP) at 10 mg/kg after oral administration, which was better than irbesartan, and the antihypertensive effect lasted beyond 24 h. These results made 1 deserve further investigation.
ISSN:1064-1963
1525-6006
DOI:10.3109/10641963.2016.1151527