Nonpeptidic angiotensin II AT1 receptor antagonists derived from 6-substituted aminocarbonyl and acylamino benzimidazoles

Jun Zhang; Jin Liang Wang; Wei Fa Yu; Zhi Ming Zhou; Wen Chang Tao; Yi Cheng Wang; Wei Zhe Xue; Di Xu; Li Ping Hao; Xiao Feng Han; Fan Fei; Ting Liu; Ai Hua Liang

doi:10.1016/j.ejmech.2013.08.014

Nonpeptidic angiotensin II AT₁ receptor antagonists derived from 6-substituted aminocarbonyl and acylamino benzimidazoles

Jun Zhang, Jin Liang Wang^*, Wei Fa Yu, Zhi Ming Zhou, Wen Chang Tao, Yi Cheng Wang, Wei Zhe Xue, Di Xu, Li Ping Hao, Xiao Feng Han, Fan Fei, Ting Liu, Ai Hua Liang

^*Corresponding author for this work

School of Chemistry and Chemical Engineering

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

24 Citations (Scopus)

Abstract

Both 6-substituted aminocarbonyl and acylamino benzimidazole derivatives were designed and synthesized as nonpeptidic angiotensin II AT₁ receptor antagonists. Compounds 6f, 6g, 11e, 11f, 11g, and 12 showed nanomolar AT₁ receptor binding affinity and high AT₁ receptor selectivity over AT₂ receptor in a preliminary pharmacological evaluation. Among them, the two most active compounds 6f (AT₁ IC ₅₀ = 3 nM, AT₂ IC₅₀ > 10,000 nM, PA ₂ = 8.51) and 11g (AT₁ IC₅₀ = 0.1 nM, AT ₂ IC₅₀ = 149 nM, PA₂ = 8.43) exhibited good antagonistic activity in isolated rabbit aortic strip functional assay. In addition, they were orally active AT₁ receptor antagonists in spontaneous hypertensive rats.

Original language	English
Pages (from-to)	44-54
Number of pages	11
Journal	European Journal of Medicinal Chemistry
Volume	69
DOIs	https://doi.org/10.1016/j.ejmech.2013.08.014
Publication status	Published - 2013

Keywords

Acylamino benzimidazole
Aminoacyl benzimidazole
Angiotensin II AT1 receptor antagonists
Hypertension

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10.1016/j.ejmech.2013.08.014

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Zhang, J., Wang, J. L., Yu, W. F., Zhou, Z. M., Tao, W. C., Wang, Y. C., Xue, W. Z., Xu, D., Hao, L. P., Han, X. F., Fei, F., Liu, T., & Liang, A. H. (2013). Nonpeptidic angiotensin II AT₁ receptor antagonists derived from 6-substituted aminocarbonyl and acylamino benzimidazoles. European Journal of Medicinal Chemistry, 69, 44-54. https://doi.org/10.1016/j.ejmech.2013.08.014

@article{41ac7942a57d46b383e2d32fc5704a0b,

title = "Nonpeptidic angiotensin II AT1 receptor antagonists derived from 6-substituted aminocarbonyl and acylamino benzimidazoles",

abstract = "Both 6-substituted aminocarbonyl and acylamino benzimidazole derivatives were designed and synthesized as nonpeptidic angiotensin II AT1 receptor antagonists. Compounds 6f, 6g, 11e, 11f, 11g, and 12 showed nanomolar AT1 receptor binding affinity and high AT1 receptor selectivity over AT2 receptor in a preliminary pharmacological evaluation. Among them, the two most active compounds 6f (AT1 IC 50 = 3 nM, AT2 IC50 > 10,000 nM, PA 2 = 8.51) and 11g (AT1 IC50 = 0.1 nM, AT 2 IC50 = 149 nM, PA2 = 8.43) exhibited good antagonistic activity in isolated rabbit aortic strip functional assay. In addition, they were orally active AT1 receptor antagonists in spontaneous hypertensive rats.",

keywords = "Acylamino benzimidazole, Aminoacyl benzimidazole, Angiotensin II AT1 receptor antagonists, Hypertension",

author = "Jun Zhang and Wang, \{Jin Liang\} and Yu, \{Wei Fa\} and Zhou, \{Zhi Ming\} and Tao, \{Wen Chang\} and Wang, \{Yi Cheng\} and Xue, \{Wei Zhe\} and Di Xu and Hao, \{Li Ping\} and Han, \{Xiao Feng\} and Fan Fei and Ting Liu and Liang, \{Ai Hua\}",

year = "2013",

doi = "10.1016/j.ejmech.2013.08.014",

language = "English",

volume = "69",

pages = "44--54",

journal = "European Journal of Medicinal Chemistry",

issn = "0223-5234",

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TY - JOUR

T1 - Nonpeptidic angiotensin II AT1 receptor antagonists derived from 6-substituted aminocarbonyl and acylamino benzimidazoles

AU - Zhang, Jun

AU - Wang, Jin Liang

AU - Yu, Wei Fa

AU - Zhou, Zhi Ming

AU - Tao, Wen Chang

AU - Wang, Yi Cheng

AU - Xue, Wei Zhe

AU - Xu, Di

AU - Hao, Li Ping

AU - Han, Xiao Feng

AU - Fei, Fan

AU - Liu, Ting

AU - Liang, Ai Hua

PY - 2013

Y1 - 2013

N2 - Both 6-substituted aminocarbonyl and acylamino benzimidazole derivatives were designed and synthesized as nonpeptidic angiotensin II AT1 receptor antagonists. Compounds 6f, 6g, 11e, 11f, 11g, and 12 showed nanomolar AT1 receptor binding affinity and high AT1 receptor selectivity over AT2 receptor in a preliminary pharmacological evaluation. Among them, the two most active compounds 6f (AT1 IC 50 = 3 nM, AT2 IC50 > 10,000 nM, PA 2 = 8.51) and 11g (AT1 IC50 = 0.1 nM, AT 2 IC50 = 149 nM, PA2 = 8.43) exhibited good antagonistic activity in isolated rabbit aortic strip functional assay. In addition, they were orally active AT1 receptor antagonists in spontaneous hypertensive rats.

AB - Both 6-substituted aminocarbonyl and acylamino benzimidazole derivatives were designed and synthesized as nonpeptidic angiotensin II AT1 receptor antagonists. Compounds 6f, 6g, 11e, 11f, 11g, and 12 showed nanomolar AT1 receptor binding affinity and high AT1 receptor selectivity over AT2 receptor in a preliminary pharmacological evaluation. Among them, the two most active compounds 6f (AT1 IC 50 = 3 nM, AT2 IC50 > 10,000 nM, PA 2 = 8.51) and 11g (AT1 IC50 = 0.1 nM, AT 2 IC50 = 149 nM, PA2 = 8.43) exhibited good antagonistic activity in isolated rabbit aortic strip functional assay. In addition, they were orally active AT1 receptor antagonists in spontaneous hypertensive rats.

KW - Acylamino benzimidazole

KW - Aminoacyl benzimidazole

KW - Angiotensin II AT1 receptor antagonists

KW - Hypertension

UR - https://www.scopus.com/pages/publications/84883252740

U2 - 10.1016/j.ejmech.2013.08.014

DO - 10.1016/j.ejmech.2013.08.014

M3 - Article

C2 - 24007859

AN - SCOPUS:84883252740

SN - 0223-5234

VL - 69

SP - 44

EP - 54

JO - European Journal of Medicinal Chemistry

JF - European Journal of Medicinal Chemistry

ER -

Nonpeptidic angiotensin II AT₁ receptor antagonists derived from 6-substituted aminocarbonyl and acylamino benzimidazoles

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Keywords

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