Discovery of Imidazopyridine Derivatives as Highly Potent Respiratory Syncytial Virus Fusion Inhibitors

被引：71
|
作者：
Feng, Song [1 ]
Hong, Di [1 ]
Wang, Baoxia [1 ]
Zheng, Xiufang [1 ]
Miao, Kun [1 ]
Wang, Lisha [2 ]
Yun, Hongying [1 ]
Gao, Lu [3 ]
Zhao, Shuhai [1 ]
Shen, Hong C. [1 ]
机构：
[1] Roche Innovat Ctr Shanghai, Med Chem, Shanghai 201203, Peoples R China
[2] Roche Innovat Ctr Shanghai, Mol Design & Chem Biol, Shanghai 201203, Peoples R China
[3] Roche Innovat Ctr Shanghai, Infect Dis Pharmaceut Res & Early Dev, Shanghai 201203, Peoples R China
来源：
ACS MEDICINAL CHEMISTRY LETTERS | 2015年 / 6卷 / 03期
关键词：
Respiratory syncytial virus (RSV); virus; antiviral; fusion inhibitors; imidazopyridine; heterocycle; OPTIMIZATION; INFLUENZA; ENTRY;
D O I：
10.1021/acsmedchemlett.5b00008
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
A series of imidazolepyridine derivatives were designed and synthesized according to the established docking studies. The imidazopyridine derivatives were found to have good potency and physical-chemical properties. Several highly potent compounds such as 8ji, 8j1, and 8jm were identified with single nanomolar activities. The most potent compound 8jrn showed an IC50 of 3 nM, lower nnicrosome clearance and no CYP inhibition. The profile of 8jrn appeared to be superior to BMS433771, and supported further optimization.
引用
收藏
页码：359 / 362
页数：4
相关论文
共 50 条
  • [31] Discovery of Flavonol derivatives as porcine reproductive and respiratory syndrome virus inhibitors
    Wang, Zhi-Zheng
    Xiao, Chen-Xu
    Huang, Wen-Li
    Hu, Yang
    Zhang, Hui-Ting
    Liu, Zhang
    Peng, Sheng-Hao
    Wei, Zigong
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2025, 121
  • [32] Small molecule inhibitors of respiratory syncytial virus
    Dyall, J
    Buscher, B
    Balsarotti, J
    Roth, R
    Starkey, G
    O'Guin, A
    Olivo, PD
    ANTIVIRAL RESEARCH, 2006, 70 (01) : A30 - A30
  • [33] Discovery of highly potent small molecule Hepatitis C Virus entry inhibitors
    Mittapalli, Gopi Kumar
    Jackson, Andrew
    Zhao, Fang
    Lee, Haekyung
    Chow, Stephine
    McKelvy, Jeffrey
    Wong-Staal, Flossie
    Macdonald, James E.
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2011, 21 (22) : 6852 - 6855
  • [34] Respiratory syncytial virus fusion inhibitors. Part 5: Optimization of benzimidazole substitution patterns towards derivatives with improved activity
    Wang, Xiangdong Alan
    Cianci, Christopher W.
    Yu, Kuo-Long
    Combrink, Keith D.
    Thuring, Jan W.
    Zhang, Yi
    Civiello, Rita L.
    Kadow, Kathleen F.
    Roach, Julia
    Li, Zhufang
    Langley, David R.
    Krystal, Mark
    Meanwell, Nicholas A.
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2007, 17 (16) : 4592 - 4598
  • [35] Discovery and optimization of phthalazinone derivatives as a new class of potent dengue virus inhibitors
    Lu, Dong
    Liu, Jianan
    Zhang, Yunzhe
    Liu, Feifei
    Zeng, Limin
    Peng, Runze
    Yang, Li
    Ying, Huazhou
    Tang, Wei
    Chen, Wuhong
    Zuo, Jianping
    Tong, Xiankun
    Liu, Tao
    Hu, Youhong
    EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2018, 145 : 328 - 337
  • [36] Discovery of a potent dual inhibitor of wild-type and mutant respiratory syncytial virus fusion proteins through the modulation of atropisomer interconversion properties
    Yamaguchi-Sasaki, Toru
    Kawaguchi, Takanori
    Okada, Atsushi
    Tokura, Seiken
    Tanaka-Yamamoto, Nozomi
    Takeuchi, Tomoki
    Ogata, Yuya
    Takahashi, Ryo
    Kurimoto-Tsuruta, Risa
    Tamaoki, Tomokazu
    Sugaya, Yutaka
    Abe-Kumasaka, Tomoko
    Arikawa, Kaho
    Yoshida, Ippei
    Sugiyama, Hiroyuki
    Kanuma, Kosuke
    Yoshinaga, Mitsukane
    BIOORGANIC & MEDICINAL CHEMISTRY, 2020, 28 (24)
  • [37] The discovery of novel, highly potent inhibitors of BRAF
    Niculescu-Duvaz, I.
    Menard, D.
    Niculescu-Duvaz, D.
    Zambon, A.
    Davies, L.
    Preece, N.
    Kirk, R.
    Whittaker, S.
    Marais, R.
    Springer, C.
    EJC SUPPLEMENTS, 2010, 8 (07): : 139 - 139
  • [38] The Story behind the Science: On the discovery of respiratory syncytial virus
    Casadevall, Arturo
    Roane, Philip R.
    Shenk, Thomas
    Roizman, Bernard
    MBIO, 2025, 16 (03)
  • [39] Discovery of furanone derivatives as potent BRAF inhibitors
    Liu, Dong
    Zhang, Jiayin
    Shen, Ru
    Yang, Liuqing
    Wang, Jianfeng
    Zhang, Lei
    Gong, Aishen
    Lu, Biao
    Yan, Yinfa
    Sun, Qiming
    Wan, Hong
    Yan, Pangke
    Zhang, Lianshan
    Cao, Jingsong
    Zhang, Minsheng
    ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2018, 255
  • [40] Discovery of a Novel Respiratory Syncytial Virus Replication Inhibitor
    Wang, Li
    Zhu, Qihui
    Xiang, Kunlun
    Zhang, Yaling
    Li, Baocun
    Yu, Xin
    Yang, Guang
    Liang, Chungen
    Yun, Hongying
    Zhang, Meifang
    Qin, Ning
    Gao, Lu
    ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2021, 65 (06)
12345