Literature DB >> 30108798

The discovery of a pan-genotypic, primer grip inhibitor of HCV NS5B polymerase.

Kyle J Eastman1, Kyle Parcella1, Kap-Sun Yeung1, Katharine A Grant-Young1, Juliang Zhu1, Tao Wang1, Zhongxing Zhang1, Zhiwei Yin1, Brett R Beno1, Steven Sheriff1, Kevin Kish1, Jeffrey Tredup1, Adam G Jardel1, Vivek Halan1, Kaushik Ghosh1, Dawn Parker1, Kathy Mosure1, Hua Fang1, Ying-Kai Wang1, Julie Lemm1, Xiaoliang Zhuo1, Umesh Hanumegowda1, Karen Rigat1, Maria Donoso1, Maria Tuttle1, Tatyana Zvyaga1, Zuzana Haarhoff1, Nicholas A Meanwell1, Matthew G Soars1, Susan B Roberts1, John F Kadow1.   

Abstract

The development of a series of novel 7-azabenzofurans exhibiting pan-genotype inhibition of HCV NS5B polymerase via binding to the primer grip site is presented. Many challenges, including poor oral bioavailability, high clearance, bioactivation, high human serum shift, and metabolic stability were encountered and overcome through SAR studies. This work culminated in the selection of BMS-986139 (43) as a preclinical candidate.

Entities:  

Year:  2017        PMID： 30108798      PMCID： PMC6072320          DOI： 10.1039/c6md00636a

Source DB:  PubMed          Journal:  Medchemcomm        ISSN： 2040-2503            Impact factor:   3.597


  11 in total

1.  Scalable synthesis of 1-bicyclo[1.1.1]pentylamine via a hydrohydrazination reaction.

Authors:  Kevin D Bunker; Neal W Sach; Qinhua Huang; Paul F Richardson
Journal:  Org Lett       Date:  2011-08-11       Impact factor: 6.005

2.  The discovery of asunaprevir (BMS-650032), an orally efficacious NS3 protease inhibitor for the treatment of hepatitis C virus infection.

Authors:  Paul M Scola; Li-Qiang Sun; Alan Xiangdong Wang; Jie Chen; Ny Sin; Brian L Venables; Sing-Yuen Sit; Yan Chen; Anthony Cocuzza; Donna M Bilder; Stanley V D'Andrea; Barbara Zheng; Piyasena Hewawasam; Yong Tu; Jacques Friborg; Paul Falk; Dennis Hernandez; Steven Levine; Chaoqun Chen; Fei Yu; Amy K Sheaffer; Guangzhi Zhai; Diana Barry; Jay O Knipe; Yong-Hae Han; Richard Schartman; Maria Donoso; Kathy Mosure; Michael W Sinz; Tatyana Zvyaga; Andrew C Good; Ramkumar Rajamani; Kevin Kish; Jeffrey Tredup; Herbert E Klei; Qi Gao; Luciano Mueller; Richard J Colonno; Dennis M Grasela; Stephen P Adams; James Loy; Paul C Levesque; Huabin Sun; Hong Shi; Lucy Sun; William Warner; Danshi Li; Jialong Zhu; Nicholas A Meanwell; Fiona McPhee
Journal:  J Med Chem       Date:  2014-03-05       Impact factor: 7.446

Review 3.  New kinetic models for the hepatitis C virus.

Authors:  Alan S Perelson; Eva Herrmann; Florence Micol; Stefan Zeuzem
Journal:  Hepatology       Date:  2005-10       Impact factor: 17.425

4.  Hepatitis C virus genotype 7, a new genotype originating from central Africa.

Authors:  Donald G Murphy; Erwin Sablon; Jasmine Chamberland; Eric Fournier; Raymond Dandavino; Cécile L Tremblay
Journal:  J Clin Microbiol       Date:  2014-12-17       Impact factor: 5.948

5.  A comparison of aroclor 1254-induced and uninduced rat liver microsomes to human liver microsomes in phenytoin O-deethylation, coumarin 7-hydroxylation, tolbutamide 4-hydroxylation, S-mephenytoin 4'-hydroxylation, chloroxazone 6-hydroxylation and testosterone 6beta-hydroxylation.

Authors:  J Easterbrook; D Fackett; A P Li
Journal:  Chem Biol Interact       Date:  2001-05-16       Impact factor: 5.192

6.  Severe hepatocellular injury with apoptosis induced by a hepatitis C polymerase inhibitor.

Authors:  Ariel Feldstein; David Kleiner; David Kravetz; Martina Buck
Journal:  J Clin Gastroenterol       Date:  2009-04       Impact factor: 3.062

7.  Discovery and initial optimization of alkoxyanthranilic acid derivatives as inhibitors of HCV NS5B polymerase.

Authors:  Kyle Parcella; Andrew Nickel; Brett R Beno; Steven Sheriff; Changhong Wan; Ying-Kai Wang; Susan B Roberts; Nicholas A Meanwell; John F Kadow
Journal:  Bioorg Med Chem Lett       Date:  2016-11-22       Impact factor: 2.823

8.  Discovery and preclinical characterization of the cyclopropylindolobenzazepine BMS-791325, a potent allosteric inhibitor of the hepatitis C virus NS5B polymerase.

Authors:  Robert G Gentles; Min Ding; John A Bender; Carl P Bergstrom; Katharine Grant-Young; Piyasena Hewawasam; Thomas Hudyma; Scott Martin; Andrew Nickel; Alicia Regueiro-Ren; Yong Tu; Zhong Yang; Kap-Sun Yeung; Xiaofan Zheng; Sam Chao; Jung-Hui Sun; Brett R Beno; Daniel M Camac; Chong-Hwan Chang; Mian Gao; Paul E Morin; Steven Sheriff; Jeff Tredup; John Wan; Mark R Witmer; Dianlin Xie; Umesh Hanumegowda; Jay Knipe; Kathy Mosure; Kenneth S Santone; Dawn D Parker; Xiaoliang Zhuo; Julie Lemm; Mengping Liu; Lenore Pelosi; Karen Rigat; Stacey Voss; Yi Wang; Ying-Kai Wang; Richard J Colonno; Min Gao; Susan B Roberts; Qi Gao; Alicia Ng; Nicholas A Meanwell; John F Kadow
Journal:  J Med Chem       Date:  2014-01-07       Impact factor: 7.446

9.  Hepatitis C virus NS5A replication complex inhibitors: the discovery of daclatasvir.

Authors:  Makonen Belema; Van N Nguyen; Carol Bachand; Dan H Deon; Jason T Goodrich; Clint A James; Rico Lavoie; Omar D Lopez; Alain Martel; Jeffrey L Romine; Edward H Ruediger; Lawrence B Snyder; Denis R St Laurent; Fukang Yang; Juliang Zhu; Henry S Wong; David R Langley; Stephen P Adams; Glenn H Cantor; Anjaneya Chimalakonda; Aberra Fura; Benjamin M Johnson; Jay O Knipe; Dawn D Parker; Kenneth S Santone; Robert A Fridell; Julie A Lemm; Donald R O'Boyle; Richard J Colonno; Min Gao; Nicholas A Meanwell; Lawrence G Hamann
Journal:  J Med Chem       Date:  2014-02-12       Impact factor: 7.446

10.  Quantifying the diversification of hepatitis C virus (HCV) during primary infection: estimates of the in vivo mutation rate.

Authors:  Ruy M Ribeiro; Hui Li; Shuyi Wang; Mark B Stoddard; Gerald H Learn; Bette T Korber; Tanmoy Bhattacharya; Jeremie Guedj; Erica H Parrish; Beatrice H Hahn; George M Shaw; Alan S Perelson
Journal:  PLoS Pathog       Date:  2012-08-23       Impact factor: 6.823
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  1 in total

1.  NMR reveals the intrinsically disordered domain 2 of NS5A protein as an allosteric regulator of the hepatitis C virus RNA polymerase NS5B.

Authors:  Luiza M Bessa; Hélène Launay; Marie Dujardin; François-Xavier Cantrelle; Guy Lippens; Isabelle Landrieu; Robert Schneider; Xavier Hanoulle
Journal:  J Biol Chem       Date:  2017-09-14       Impact factor: 5.486
  1 in total

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