Allosteric inhibitors of hepatitis C polymerase: Discovery of potent and orally bioavailable carbon-linked dihydropyrones

被引：36

作者：

Li, Hui ^{[1
]}

Linton, Angelica ^{[1
]}

Tatlock, John ^{[1
]}

Gonzalez, Javier ^{[1
]}

Borchardt, Allen ^{[1
]}

Abreo, Mel ^{[1
]}

Jewell, Tanya ^{[1
]}

Patel, Leena ^{[1
]}

Drowns, Matthew ^{[1
]}

Ludlum, Sarah ^{[1
]}

Goble, Mike ^{[1
]}

Yang, Michele ^{[1
]}

Blazel, Julie ^{[1
]}

Rahavendran, Ravi ^{[1
]}

Skor, Heather ^{[1
]}

Shi, Stephanie ^{[1
]}

Lewis, Cristina ^{[1
]}

Fuhrman, Shella ^{[1
]}

机构：

[1] Pfizer Global Res & Dev, La Jolla Labs, San Diego, CA 92121 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2007年 / 50卷 / 17期

关键词：

D O I：

10.1021/jm0704447

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The discovery and optimization of a novel class of carbon-linked dihydropyrones as allosteric HCV NS5B polymerase inhibitors are presented. Replacement of the sulfur linker atom with carbon reduced compound acidity and greatly increased cell permeation. Further structure-activity relationship (SAR) studies led to the identification of compounds, exemplified by 23 and 24, with significantly improved antiviral activities in the cell-based replicon assay and favorable pharmacokinetic profiles.

引用

页码：3969 / 3972

页数：4

共 50 条

[31] Discovery of potent and selective orally bioavailable β-substituted phenylalanine derived dipeptidyl peptidase IV inhibitors
Edmondson, SD
Mastracchio, A
Duffy, JL
Eiermann, GJ
He, HB
Ita, I
Leiting, B
Leone, JF
Lyons, KA
Makarewicz, AM
Patel, RA
Petrov, A
Wu, JK
Nancy, AT
Weber, AE
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2005, 15 (12) : 3048 - 3052
[32] Discovery of orally bioavailable phosphonate prodrugs of potent ENPP1 inhibitors for cancer treatment
Gao, Shanyun
Hou, Yingjie
Xu, Yanxiao
Li, Jingjing
Zhang, Chaobo
Jiang, Shujuan
Yu, Songda
Liu, Lei
Tu, Wangyang
Yu, Bing
Zhang, Yixiang
Li, Leping
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2024, 279
[33] The discovery of potent, selective, and orally bioavailable PDE9 inhibitors as potential hypoglycemic agents
DeNinno, Michael P.
Andrews, Melissa
Bell, Andrew S.
Chen, Yue
Eller-Zarbo, Cynthia
Eshelby, Nan
Etienne, John B.
Moore, Dianna E.
Palmer, Michael J.
Visser, Michael S.
Yu, Li J.
Zavadoski, William J.
Gibbs, E. Michael
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2009, 19 (09) : 2537 - 2541
[34] From PROTAC to inhibitor: Structure-guided discovery of potent and orally bioavailable BET inhibitors
Koravovic, Mladen
Mayasundari, Anand
Tasic, Gordana
Keramatnia, Fatemeh
Stachowski, Timothy R.
Cui, Huarui
Chai, Sergio C.
Jonchere, Barbara
Yang, Lei
Li, Yong
Fu, Xiang
Hiltenbrand, Ryan
Paul, Leena
Mishra, Vibhor
Klco, Jeffery M.
Roussel, Martine F.
Pomerantz, William CK.
Fischer, Marcus
Rankovic, Zoran
Savic, Vladimir
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2023, 251
[35] Discovery of Potent, Selective, and Orally Bioavailable DYRK2 Inhibitors for the Treatment of Prostate Cancer
Yuan, Kai
Xia, Fei
Li, Qiannan
Zheng, Mingming
Shen, Hongtao
Chen, Weijiao
Yang, Huanaoyu
Zhuang, Xujie
Zhang, Xiao-Yu
Xiao, Yibei
Yang, Peng
JOURNAL OF MEDICINAL CHEMISTRY, 2023, 66 (23) : 16235 - 16256
[36] Discovery of 3-aminopiperidines as potent, selective, and orally bioavailable dipeptidyl peptidase IV inhibitors
Cox, Jason M.
Harper, Bart
Mastracchio, Anthony
Leiting, Barbara
Roy, Ranabir Sinha
Patel, Reshma A.
Wu, Joseph K.
Lyons, Kathryn A.
He, Huaibing
Xu, Shiyao
Zhu, Bing
Thornberry, Nancy A.
Weber, Ann E.
Edmondson, Scott D.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2007, 17 (16) : 4579 - 4583
[37] Selective Inhibitors of the Mutant B-Raf Pathway: Discovery of a Potent and Orally Bioavailable Aminoisoquinoline
Smith, Adrian L.
DeMorin, Frenel F.
Paras, Nick A.
Huang, Qi
Petkus, Jeffrey K.
Doherty, Elizabeth M.
Nixey, Thomas
Kim, Joseph L.
Whittington, Douglas A.
Epstein, Linda F.
Lee, Matthew R.
Rose, Mark J.
Babij, Carol
Fernando, Manory
Hess, Kristen
Le, Quynh
Beltran, Pedro
Carnahan, Josette
JOURNAL OF MEDICINAL CHEMISTRY, 2009, 52 (20) : 6189 - 6192
[38] Discovery of potent, selective, and orally bioavailable oxadiazole-based dipeptidyl peptidase IV inhibitors
Xu, Jinyou
Wei, Lan
Mathvink, Robert J.
Edmondson, Scott D.
Eiermann, George J.
He, Huaibing
Leone, Joseph F.
Leiting, Barbara
Lyons, Kathryn A.
Marsilio, Frank
Patel, Reshma A.
Patel, Sangita B.
Petrov, Aleksandr
Scapin, Giovanna
Wu, Joseph K.
Thornberry, Nancy A.
Weber, Ann E.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2006, 16 (20) : 5373 - 5377
[39] MEDI 196-Discovery of novel, potent, and orally bioavailable STAT6 inhibitors
Nagashima, Shinya
Nagata, Hiroshi
Iwata, Masahiro
Yokota, Masaki
Moritomo, Hiroyuki
Kuromitsu, Sadao
Ohga, Keiko
Takeuchi, Makoto
Tsukamoto, Shin-ichi
Ohta, Mitsuaki
ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2006, 232
[40] Novel, potent and orally bioavailable indolizidinone-derived inhibitors of the hepatitis C virus NS3 protease
Clarke, Michael O.
Byun, Daniel
Chen, Xiaowu
Doerffler, Edward
Leavitt, Stephanie A.
Sheng, X. Christopher
Yang, Cheng Y.
Kim, Choung U.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2012, 22 (02) : 1095 - 1098

← 1 2 3 4 5 →