Synthesis and biological evaluation of 4′-[(benzimidazole-1-yl) methyl]biphenyl-2-sulfonamide derivatives as dual angiotensin II/endothelin A receptor antagonists

Renren Bai; Zhen Wei; Jie Liu; Weijia Xie; Hequan Yao; Xiaoming Wu; Jieyun Jiang; Qiujuan Wang; Jinyi Xu

doi:10.1016/j.bmc.2012.06.011

Synthesis and biological evaluation of 4′-[(benzimidazole-1-yl) methyl]biphenyl-2-sulfonamide derivatives as dual angiotensin II/endothelin A receptor antagonists

Renren Bai
, Zhen Wei
, Jie Liu
, Weijia Xie
, Hequan Yao
, Xiaoming Wu
, Jieyun Jiang
, Qiujuan Wang
, Jinyi Xu

Microbiology, Immunology, and Molecular Genetics

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

26 Scopus citations

Abstract

A series of 4′-[(benzimidazole-1-yl)methyl]biphenyl-2-sulfonamide derivatives (Ia-Il) were synthesized and biologically evaluated. It was found that Ig, the most active compound, antagonized both Ang II AT₁ and endothelin ET_A receptors (AT₁ IC₅₀ = 8.5, ET_A IC₅₀ = 8.9 nM), and was more potent than losartan in RHRs with no significant effect on heart rate. The preliminary structure-activity relationships were also discussed in the present paper.

Original language	English
Pages (from-to)	4661-4667
Number of pages	7
Journal	Bioorganic and Medicinal Chemistry
Volume	20
Issue number	15
DOIs	https://doi.org/10.1016/j.bmc.2012.06.011
State	Published - Aug 1 2012

Bibliographical note

Funding Information:
This study was financially supported by grant from ‘Eleventh Five-Year’ Major Innovation Projects for New Drug Candidates (No. 2009ZX09102-036), Jiangsu Provincial Science Fund (No. BK2008344) and Project for Research and Innovation of Graduates in Colleges and Universities of Jiangsu Province (CXZZ11-0798).

Funding

This study was financially supported by grant from ‘Eleventh Five-Year’ Major Innovation Projects for New Drug Candidates (No. 2009ZX09102-036), Jiangsu Provincial Science Fund (No. BK2008344) and Project for Research and Innovation of Graduates in Colleges and Universities of Jiangsu Province (CXZZ11-0798).

Funders
Jiangsu Provincial Science Fund

Keywords

AT receptor
Antihypertensive activity
DARAs
ET receptor
Structure-activity relationships

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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10.1016/j.bmc.2012.06.011

Cite this

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title = "Synthesis and biological evaluation of 4′-[(benzimidazole-1-yl) methyl]biphenyl-2-sulfonamide derivatives as dual angiotensin II/endothelin A receptor antagonists",

abstract = "A series of 4′-[(benzimidazole-1-yl)methyl]biphenyl-2-sulfonamide derivatives (Ia-Il) were synthesized and biologically evaluated. It was found that Ig, the most active compound, antagonized both Ang II AT1 and endothelin ETA receptors (AT1 IC50 = 8.5, ETA IC50 = 8.9 nM), and was more potent than losartan in RHRs with no significant effect on heart rate. The preliminary structure-activity relationships were also discussed in the present paper.",

keywords = "AT receptor, Antihypertensive activity, DARAs, ET receptor, Structure-activity relationships",

author = "Renren Bai and Zhen Wei and Jie Liu and Weijia Xie and Hequan Yao and Xiaoming Wu and Jieyun Jiang and Qiujuan Wang and Jinyi Xu",

note = "Funding Information: This study was financially supported by grant from {\textquoteleft}Eleventh Five-Year{\textquoteright} Major Innovation Projects for New Drug Candidates (No. 2009ZX09102-036), Jiangsu Provincial Science Fund (No. BK2008344) and Project for Research and Innovation of Graduates in Colleges and Universities of Jiangsu Province (CXZZ11-0798).",

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doi = "10.1016/j.bmc.2012.06.011",

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AU - Bai, Renren

AU - Wei, Zhen

AU - Liu, Jie

AU - Xie, Weijia

AU - Yao, Hequan

AU - Wu, Xiaoming

AU - Jiang, Jieyun

AU - Wang, Qiujuan

AU - Xu, Jinyi

N1 - Funding Information: This study was financially supported by grant from ‘Eleventh Five-Year’ Major Innovation Projects for New Drug Candidates (No. 2009ZX09102-036), Jiangsu Provincial Science Fund (No. BK2008344) and Project for Research and Innovation of Graduates in Colleges and Universities of Jiangsu Province (CXZZ11-0798).

PY - 2012/8/1

Y1 - 2012/8/1

N2 - A series of 4′-[(benzimidazole-1-yl)methyl]biphenyl-2-sulfonamide derivatives (Ia-Il) were synthesized and biologically evaluated. It was found that Ig, the most active compound, antagonized both Ang II AT1 and endothelin ETA receptors (AT1 IC50 = 8.5, ETA IC50 = 8.9 nM), and was more potent than losartan in RHRs with no significant effect on heart rate. The preliminary structure-activity relationships were also discussed in the present paper.

AB - A series of 4′-[(benzimidazole-1-yl)methyl]biphenyl-2-sulfonamide derivatives (Ia-Il) were synthesized and biologically evaluated. It was found that Ig, the most active compound, antagonized both Ang II AT1 and endothelin ETA receptors (AT1 IC50 = 8.5, ETA IC50 = 8.9 nM), and was more potent than losartan in RHRs with no significant effect on heart rate. The preliminary structure-activity relationships were also discussed in the present paper.

KW - AT receptor

KW - Antihypertensive activity

KW - DARAs

KW - ET receptor

KW - Structure-activity relationships

UR - https://www.scopus.com/pages/publications/84863980674

UR - https://www.scopus.com/pages/publications/84863980674#tab=citedBy

U2 - 10.1016/j.bmc.2012.06.011

DO - 10.1016/j.bmc.2012.06.011

M3 - Article

C2 - 22750010

AN - SCOPUS:84863980674

SN - 0968-0896

VL - 20

SP - 4661

EP - 4667

JO - Bioorganic and Medicinal Chemistry

JF - Bioorganic and Medicinal Chemistry

IS - 15

ER -

Synthesis and biological evaluation of 4′-[(benzimidazole-1-yl) methyl]biphenyl-2-sulfonamide derivatives as dual angiotensin II/endothelin A receptor antagonists

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

Access to Document

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