Literature DB >> 29456794

Discovery of 3,3'-Spiro[Azetidine]-2-oxo-indoline Derivatives as Fusion Inhibitors for Treatment of RSV Infection.

Weihua Shi1, Zhigan Jiang1, Haiying He1, Fubiao Xiao1, Fusen Lin1, Ya Sun1, Lijuan Hou1, Liang Shen1, Lixia Han1, Minggao Zeng1, Kunmin Lai1, Zhengxian Gu1, Xinsheng Chen1, Tao Zhao2, Li Guo2, Chun Yang2, Jian Li1, Shuhui Chen1.   

Abstract

A new series of 3,3'-spirocyclic-2-oxo-indoline derivatives was synthesized and evaluated against respiratory syncytial virus (RSV) in a cell-based assay and animal model. Extensive structure-activity relationship study led to a lead compound 14h, which exhibited excellent in vitro potency with an EC50 value of 0.8 nM and demonstrated 71% oral bioavailability in mice. In a mouse challenge model of RVS infection, 14h demonstrated superior efficacy with a 3.9log RSV virus load reduction in the lung following an oral dose of 50 mg/kg.

Entities:  

Year:  2018        PMID： 29456794      PMCID： PMC5807868          DOI： 10.1021/acsmedchemlett.7b00418

Source DB:  PubMed          Journal:  ACS Med Chem Lett        ISSN： 1948-5875            Impact factor:   4.345


  11 in total

1.  Discovery of methylsulfonyl indazoles as potent and orally active respiratory syncytial Virus(RSV) fusion inhibitors.

Authors:  Song Feng; Chao Li; Dongdong Chen; Xiufang Zheng; Hongying Yun; Lu Gao; Hong C Shen
Journal:  Eur J Med Chem       Date:  2017-07-20       Impact factor: 6.514

2.  Selection of a respiratory syncytial virus fusion inhibitor clinical candidate. 2. Discovery of a morpholinopropylaminobenzimidazole derivative (TMC353121).

Authors:  Jean-François Bonfanti; Christophe Meyer; Frédéric Doublet; Jérôme Fortin; Philippe Muller; Laurence Queguiner; Tom Gevers; Peggy Janssens; Heidi Szel; Rudy Willebrords; Philip Timmerman; Koen Wuyts; Pieter van Remoortere; Frans Janssens; Piet Wigerinck; Koen Andries
Journal:  J Med Chem       Date:  2008-02-07       Impact factor: 7.446

3.  Effect of cathepsin K inhibitors on bone resorption.

Authors:  Naoki Teno; Keiichi Masuya; Takeru Ehara; Takatoshi Kosaka; Takahiro Miyake; Osamu Irie; Yuko Hitomi; Naoko Matsuura; Ichiro Umemura; Genji Iwasaki; Hiroaki Fukaya; Kazuhiro Toriyama; Noriko Uchiyama; Kazuhiko Nonomura; Ikuo Sugiyama; Motohiko Kometani
Journal:  J Med Chem       Date:  2008-08-16       Impact factor: 7.446

4.  Respiratory syncytial virus market.

Authors:  Shane Storey
Journal:  Nat Rev Drug Discov       Date:  2010-01       Impact factor: 84.694

5.  Discovery of imidazopyridine derivatives as highly potent respiratory syncytial virus fusion inhibitors.

Authors:  Song Feng; Di Hong; Baoxia Wang; Xiufang Zheng; Kun Miao; Lisha Wang; Hongying Yun; Lu Gao; Shuhai Zhao; Hong C Shen
Journal:  ACS Med Chem Lett       Date:  2015-01-25       Impact factor: 4.345

6.  Oral GS-5806 activity in a respiratory syncytial virus challenge study.

Authors:  John P DeVincenzo; Richard J Whitley; Richard L Mackman; Cecilia Scaglioni-Weinlich; Lisa Harrison; Eric Farrell; Stephen McBride; Robert Lambkin-Williams; Robert Jordan; Yan Xin; Srini Ramanathan; Thomas O'Riordan; Sandra A Lewis; Xiaoming Li; Seth L Toback; Shao-Lee Lin; Jason W Chien
Journal:  N Engl J Med       Date:  2014-08-21       Impact factor: 91.245

7.  Discovery of an oral respiratory syncytial virus (RSV) fusion inhibitor (GS-5806) and clinical proof of concept in a human RSV challenge study.

Authors:  Richard L Mackman; Michael Sangi; David Sperandio; Jay P Parrish; Eugene Eisenberg; Michel Perron; Hon Hui; Lijun Zhang; Dustin Siegel; Hai Yang; Oliver Saunders; Constantine Boojamra; Gary Lee; Dharmaraj Samuel; Kerim Babaoglu; Anne Carey; Brian E Gilbert; Pedro A Piedra; Robert Strickley; Quynh Iwata; Jaclyn Hayes; Kirsten Stray; April Kinkade; Dorothy Theodore; Robert Jordan; Manoj Desai; Tomas Cihlar
Journal:  J Med Chem       Date:  2015-01-27       Impact factor: 7.446

8.  Respiratory syncytial virus fusion inhibitors. Part 4: optimization for oral bioavailability.

Authors:  Kuo-Long Yu; Ny Sin; Rita L Civiello; X Alan Wang; Keith D Combrink; H Belgin Gulgeze; Brian L Venables; J J Kim Wright; Richard A Dalterio; Lisa Zadjura; Anthony Marino; Sandra Dando; Celia D'Arienzo; Kathleen F Kadow; Christopher W Cianci; Zhufang Li; Junius Clarke; Eugene V Genovesi; Ivette Medina; Lucinda Lamb; Richard J Colonno; Zheng Yang; Mark Krystal; Nicholas A Meanwell
Journal:  Bioorg Med Chem Lett       Date:  2006-12-01       Impact factor: 2.823

9.  Discovery of a new class of potent, selective, and orally bioavailable CRTH2 (DP2) receptor antagonists for the treatment of allergic inflammatory diseases.

Authors:  Stefano Crosignani; Patrick Page; Marc Missotten; Véronique Colovray; Christophe Cleva; Jean-François Arrighi; John Atherall; Jackie Macritchie; Thierry Martin; Yves Humbert; Marilène Gaudet; Doris Pupowicz; Maurizio Maio; Pierre-André Pittet; Lucia Golzio; Claudio Giachetti; Cynthia Rocha; Gérald Bernardinelli; Yaroslav Filinchuk; Alexander Scheer; Matthias K Schwarz; André Chollet
Journal:  J Med Chem       Date:  2008-03-05       Impact factor: 7.446

10.  The burden of respiratory syncytial virus infection in young children.

Authors:  Caroline Breese Hall; Geoffrey A Weinberg; Marika K Iwane; Aaron K Blumkin; Kathryn M Edwards; Mary A Staat; Peggy Auinger; Marie R Griffin; Katherine A Poehling; Dean Erdman; Carlos G Grijalva; Yuwei Zhu; Peter Szilagyi
Journal:  N Engl J Med       Date:  2009-02-05       Impact factor: 91.245
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  3 in total

1.  Discovery of a Potent Dual Inhibitor of Wild-Type and Mutant Respiratory Syncytial Virus Fusion Proteins.

Authors:  Toru Yamaguchi-Sasaki; Seiken Tokura; Yuya Ogata; Takanori Kawaguchi; Yutaka Sugaya; Ryo Takahashi; Kanako Iwakiri; Tomoko Abe-Kumasaka; Ippei Yoshida; Kaho Arikawa; Hiroyuki Sugiyama; Kosuke Kanuma
Journal:  ACS Med Chem Lett       Date:  2020-04-10       Impact factor: 4.345

2.  Substituted N-(4-amino-2-chlorophenyl)-5-chloro-2-hydroxybenzamide analogues potently inhibit respiratory syncytial virus (RSV) replication and RSV infection-associated inflammatory responses.

Authors:  Jimin Xu; Wenzhe Wu; Haiying Chen; Yu Xue; Xiaoyong Bao; Jia Zhou
Journal:  Bioorg Med Chem       Date:  2021-04-18       Impact factor: 3.461

Review 3.  Characterization of Pathogenic Sepsis Etiologies and Patient Profiles: A Novel Approach to Triage and Treatment.

Authors:  Hallie H Dolin; Thomas J Papadimos; Xiaohuan Chen; Zhixing K Pan
Journal:  Microbiol Insights       Date:  2019-01-27
  3 in total

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