Design, synthesis, and biological evaluation of 1,2,4-triazole bearing 5-substituted biphenyl-2-sulfonamide derivatives as potential antihypertensive candidates

Jie Liu; Qin Liu; Xue Yang; Shengtao Xu; Hengyuan Zhang; Renren Bai; Hequan Yao; Jieyun Jiang; Mingqin Shen; Xiaoming Wu; Jinyi Xu

doi:10.1016/j.bmc.2013.10.017

Design, synthesis, and biological evaluation of 1,2,4-triazole bearing 5-substituted biphenyl-2-sulfonamide derivatives as potential antihypertensive candidates

Jie Liu, Qin Liu, Xue Yang, Shengtao Xu, Hengyuan Zhang, Renren Bai, Hequan Yao, Jieyun Jiang, Mingqin Shen, Xiaoming Wu, Jinyi Xu

Microbiology, Immunology, and Molecular Genetics

Research output: Contribution to journal › Article › peer-review

51 Scopus citations

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
Pages (from-to)	7742-7751
Number of pages	10
Journal	Bioorganic and Medicinal Chemistry
Volume	21
Issue number	24
DOIs	https://doi.org/10.1016/j.bmc.2013.10.017
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

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title = "Design, synthesis, and biological evaluation of 1,2,4-triazole bearing 5-substituted biphenyl-2-sulfonamide derivatives as potential antihypertensive candidates",

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.",

keywords = "AT receptor, Agonists, Antihypertensive activity, Biphenyl-2-sulfonamide derivatives, Structure-activity relationships",

author = "Jie Liu and Qin Liu and Xue Yang and Shengtao Xu and Hengyuan Zhang and Renren Bai and Hequan Yao and Jieyun Jiang and Mingqin Shen and Xiaoming Wu and Jinyi Xu",

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 ). ",

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doi = "10.1016/j.bmc.2013.10.017",

language = "English",

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Liu, J, Liu, Q, Yang, X, Xu, S, Zhang, H, Bai, R, Yao, H, Jiang, J, Shen, M, Wu, X & Xu, J 2013, 'Design, synthesis, and biological evaluation of 1,2,4-triazole bearing 5-substituted biphenyl-2-sulfonamide derivatives as potential antihypertensive candidates', Bioorganic and Medicinal Chemistry, vol. 21, no. 24, pp. 7742-7751. https://doi.org/10.1016/j.bmc.2013.10.017

TY - JOUR

T1 - Design, synthesis, and biological evaluation of 1,2,4-triazole bearing 5-substituted biphenyl-2-sulfonamide derivatives as potential antihypertensive candidates

AU - Liu, Jie

AU - Liu, Qin

AU - Yang, Xue

AU - Xu, Shengtao

AU - Zhang, Hengyuan

AU - Bai, Renren

AU - Yao, Hequan

AU - Jiang, Jieyun

AU - Shen, Mingqin

AU - Wu, Xiaoming

AU - Xu, Jinyi

N1 - 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 ).

PY - 2013/12/15

Y1 - 2013/12/15

N2 - 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.

AB - 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.

KW - AT receptor

KW - Agonists

KW - Antihypertensive activity

KW - Biphenyl-2-sulfonamide derivatives

KW - Structure-activity relationships

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Design, synthesis, and biological evaluation of 1,2,4-triazole bearing 5-substituted biphenyl-2-sulfonamide derivatives as potential antihypertensive candidates

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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