Discovery of GS-9451: An acid inhibitor of the hepatitis C virus NS3/4A protease

被引：33

作者：

Sheng, X. Christopher ^{[1
]}

Appleby, Todd ^{[1
]}

Butler, Thomas ^{[1
]}

Cai, Ruby ^{[1
]}

Chen, Xiaowu ^{[1
]}

Cho, Aesop ^{[1
]}

Clarke, Michael O. ^{[1
]}

Cottell, Jeromy ^{[1
]}

Delaney, William E. ^{[1
]}

Doerffler, Edward ^{[1
]}

Link, John ^{[1
]}

Ji, Mingzhe ^{[1
]}

Pakdaman, Rowchanak ^{[1
]}

Pyun, Hyung-Jung ^{[1
]}

Wu, Qiaoyin ^{[1
]}

Xu, Jie ^{[1
]}

Kim, Choung U. ^{[1
]}

机构：

[1] Gilead Sci Inc, Foster City, CA 94404 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2012年 / 22卷 / 07期

关键词：

HCV; GS-9451; NS3; Protease; Solubilizing group; INFECTION;

D O I：

10.1016/j.bmcl.2012.01.017

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The discovery of GS-9451 is reported. Modification of the P3 cap and P2 quinoline with a series of solubilizing groups led to the identification of potent HCV NS3 protease inhibitors with greatly improved pharmacokinetic properties in rats, dogs and monkeys. (C) 2012 Elsevier Ltd. All rights reserved.

引用

页码：2629 / 2634

页数：6

共 16 条

[1]

Chen Kevin X, 2008, ACCOUNTS CHEM RES, V41, P1

[2] ISOLATION OF A CDNA CLONE DERIVED FROM A BLOOD-BORNE NON-A, NON-B VIRAL-HEPATITIS GENOME [J].

CHOO, QL ;

KUO, G ;

WEINER, AJ ;

OVERBY, LR ;

BRADLEY, DW ;

HOUGHTON, M .

SCIENCE, 1989, 244 (4902) :359-362

[3]

d Irena Melnikova, 2011, NAT REV DRUG DISCOV, V10, P94

[4] Challenges and successes in developing new therapies for hepatitis C [J].

De Francesco, R ;

Migliaccio, G .

NATURE, 2005, 436 (7053) :953-960

[5] Potent inhibitors of the hepatitis C virus NS3 protease:: Design and synthesis of macrocyclic substrate-based β-strand mimics [J].

Goudreau, N ;

Brochu, C ;

Cameron, DR ;

Duceppe, JS ;

Faucher, AM ;

Ferland, JM ;

Grand-Maître, C ;

Poirier, M ;

Simoneau, B ;

Tsantrizos, YS .

JOURNAL OF ORGANIC CHEMISTRY, 2004, 69 (19) :6185-6201

[6] Telaprevir for Previously Untreated Chronic Hepatitis C Virus Infection [J].

Jacobson, Ira M. ;

McHutchison, John G. ;

Dusheiko, Geoffrey ;

Di Bisceglie, Adrian M. ;

Reddy, K. Rajender ;

Bzowej, Natalie H. ;

Marcellin, Patrick ;

Muir, Andrew J. ;

Ferenci, Peter ;

Flisiak, Robert ;

George, Jacob ;

Rizzetto, Mario ;

Shouval, Daniel ;

Sola, Ricard ;

Terg, Ruben A. ;

Yoshida, Eric M. ;

Adda, Nathalie ;

Bengtsson, Leif ;

Sankoh, Abdul J. ;

Kieffer, Tara L. ;

George, Shelley ;

Kauffman, Robert S. ;

Zeuzem, Stefan .

NEW ENGLAND JOURNAL OF MEDICINE, 2011, 364 (25) :2405-2416

[7]

Jensen DM, 2008, ANTIVIR THER, V13, P31

[8]

Kwong AD, 2008, CURR OPIN PHARMACOL, V8, P1

[9] An NS3 protease inhibitor with antiviral effects in humans infected with hepatitis C virus [J].

Lamarre, D ;

Anderson, PC ;

Bailey, M ;

Beaulieu, P ;

Bolger, G ;

Bonneau, P ;

Bös, M ;

Cameron, DR ;

Cartier, M ;

Cordingley, MG ;

Faucher, AM ;

Goudreau, N ;

Kawai, SH ;

Kukolj, G ;

Lagacé, L ;

LaPlante, SR ;

Narjes, H ;

Poupart, MA ;

Rancourt, J ;

Sentjens, RE ;

St George, R ;

Simoneau, B ;

Steinmann, G ;

Thibeault, D ;

Tsantrizos, YS ;

Weldon, SM ;

Yong, CL ;

Llinàs-Brunet, M .

NATURE, 2003, 426 (6963) :186-189

[10]

LaPlante Steven R., 2005, Current Medicinal Chemistry - Anti-Infective Agents, V4, P111, DOI 10.2174/1568012053507016

← 1 2 →