Synthesis, biological evaluation and SAR studies of benzimidazole derivatives as H1-antihistamine agents

被引：78

作者：

Wang, Xiao Jian ^{[1
,3
]}

Xi, Mei Yang ^{[2
]}

Fu, Ji Hua ^{[2
]}

Zhang, Fu Rong ^{[1
,3
]}

Cheng, Gui Fang ^{[1
,3
]}

Yin, Da Li ^{[1
,3
]}

You, Qi Dong ^{[2
]}

机构：

[1] Peking Union Med Coll, Beijing Key Lab Act Subst Discovery & Drugabil Ev, State Key Lab Bioact Subst & Funct Nat Med, Dept Med Chem,Inst Mat Med, Beijing 100050, Peoples R China

[2] China Pharmaceut Univ, Sch Pharm, Nanjing 210009, Jiangsu, Peoples R China

[3] Chinese Acad Med Sci, Beijing 100050, Peoples R China

来源：

CHINESE CHEMICAL LETTERS | 2012年 / 23卷 / 06期

关键词：

Benzimidazole derivatives; Antihistamine activity; SAR; Anti-PAF activity; hERG; HISTAMINE-RECEPTOR; PHARMACOLOGICAL CHARACTERIZATION; CLONING; EXPRESSION; CHANNELS; CELLS; ANTAGONISTS; ASTEMIZOLE; BINDING;

D O I：

10.1016/j.cclet.2012.04.020

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

A series of benzimidazole derivatives have been designed, synthesized and evaluated for H-1 antihistamine activity. Six compounds have showed potent antihistamine H-1 activity. The primary SAR analysis indicated that benzyl or benzylidinyl substituted on the exo-nitrogen atom and C2 of the benzimidazole were significant. Further experiments indicated that compound 17d displayed excellent activity to reduce mast cell degranulation, moderate anti-PAF activity and decreased potency on hERG compared to astermizole. Hence compound 17d could serve as anti-allergic agent for further development. (C) 2012 Da Li Yin. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.

引用

页码：707 / 710

页数：4

共 17 条

[1] SYNTHESIS OF THE SELECTIVE MUSCARINIC AGONIST (3R)-3-(6-CHLOROPYRAZIN-2-YL)-1-AZABICYCLO[2.2.2]OCTANE [J].