Abstract
A series of novel 1,2,4-triazole bearing 5-substituted biphenyl-2- sulfonamide derivatives were designed and synthesized to develop new angiotensin II subtype 2 (AT2) receptor agonists as novel antihypertensive candidates. It was found that 14f (IC50 = 0.4 nM) and 15e (IC 50 = 5.0 nM) displayed potent AT2 receptor affinity and selectivity in binding assays. Biological evaluation in vivo suggested that 14f is obviously superior to that of reference drug losartan in RHRs, and meanwhile, 14f has no significant impact on heart rate. The interesting activities of these compounds may make them promising candidates as antihypertensive agents.
Original language | English |
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Pages (from-to) | 7742-7751 |
Number of pages | 10 |
Journal | Bioorganic and Medicinal Chemistry |
Volume | 21 |
Issue number | 24 |
DOIs | |
State | Published - Dec 15 2013 |
Bibliographical note
Funding Information:This study was financially supported by a grant from National Natural Science Fund (No. 81302635 ) and Project Program of State Key Laboratory of Natural Medicines, China Pharmaceutical University ( JKGQ201115 ).
Keywords
- AT receptor
- Agonists
- Antihypertensive activity
- Biphenyl-2-sulfonamide derivatives
- Structure-activity relationships
ASJC Scopus subject areas
- Biochemistry
- Molecular Medicine
- Molecular Biology
- Pharmaceutical Science
- Drug Discovery
- Clinical Biochemistry
- Organic Chemistry