Discovery of thiophene-2-carboxylic acids as potent inhibitors of HCVNS5B polymerase and HCV subgenomic RNA replication.: Part 2:: Tertiary amides

被引：92

作者：

Chan, L ^{[1
]}

Pereira, O ^{[1
]}

Reddy, TJ ^{[1
]}

Das, SK ^{[1
]}

Poisson, C ^{[1
]}

Courchesne, M ^{[1
]}

Proulx, M ^{[1
]}

Siddiqui, A ^{[1
]}

Yannopoulos, CG ^{[1
]}

Nguyen-Ba, N ^{[1
]}

Roy, C ^{[1
]}

Nasturica, D ^{[1
]}

Moinet, C ^{[1
]}

Bethell, R ^{[1
]}

Hamel, M ^{[1
]}

L'Heureux, L ^{[1
]}

David, M ^{[1
]}

Nicolas, O ^{[1
]}

Courtemanche-Asselin, P ^{[1
]}

Brunette, S ^{[1
]}

Bilimoria, D ^{[1
]}

Bédard, J ^{[1
]}

机构：

[1] Shire BioChem Inc, Laval, PQ H7V 4A7, Canada

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2004年 / 14卷 / 03期

关键词：

D O I：

10.1016/j.bmcl.2003.10.068

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Further SAR studies on the thiophene-2-carboxylic acids are reported. These studies led to the identification of a series of tertiary amides that show inhibition of both HCV NS5B polymerase in vitro and HCV subgenomic RNA replication in Huh-7 cells. Structural insights about the bioactive conformation of this class of molecules were deduced from a combination of modeling and transferred NOE (trNOE) studies. (C) 2003 Elsevier Ltd. All rights reserved.

引用

页码：797 / 800

页数：4

共 9 条

[1] Hepatitis C virus replicons: potential role for drug development
Bartenschlager, R
[J]. NATURE REVIEWS DRUG DISCOVERY, 2002, 1 (11) : 911 - 916
[2] Identification of N,N-disubstituted phenylalanines as a novel class of inhibitors of hepatitis CNS5B polymerase
Chan, L
Reddy, TJ
Proulx, M
Das, SK
Pereira, O
Wang, WY
Siddiqui, A
Yannopoulos, CG
Poisson, C
Turcotte, N
Drouin, A
Alaoui-Ismaili, MH
Bethell, R
Hamel, M
L'Heureux, L
Bilimoria, D
Nguyen-Ba, N
[J]. JOURNAL OF MEDICINAL CHEMISTRY, 2003, 46 (08) : 1283 - 1285
[3] CHAN L, 2004, BIOORG MED CHEM LETT, P14, DOI DOI 10.1016/J.BMCL.2003.10.068
[4] THEORY AND APPLICATIONS OF THE TRANSFERRED NUCLEAR OVERHAUSER EFFECT TO THE STUDY OF THE CONFORMATIONS OF SMALL LIGANDS BOUND TO PROTEINS
CLORE, GM
GRONENBORN, AM
[J]. JOURNAL OF MAGNETIC RESONANCE, 1982, 48 (03) : 402 - 417
[5] N-methylated cyclic RGD peptides as highly active and selective αvβ3 integrin antagonists
Dechantsreiter, MA
Planker, E
Mathä, B
Lohof, E
Hölzemann, G
Jonczyk, A
Goodman, SL
Kessler, H
[J]. JOURNAL OF MEDICINAL CHEMISTRY, 1999, 42 (16) : 3033 - 3040
[6] Hepatitis C: an epidemiological review
Memon, MI
Memon, MA
[J]. JOURNAL OF VIRAL HEPATITIS, 2002, 9 (02) : 84 - 100
[7] USE OF THE TRANSFERRED NUCLEAR OVERHAUSER EFFECT TO DETERMINE THE CONFORMATIONS OF LIGANDS BOUND TO PROTEINS
NI, F
SCHERAGA, HA
[J]. ACCOUNTS OF CHEMICAL RESEARCH, 1994, 27 (09) : 257 - 264
[8] Modulation of the hepatitis C virus RNA-dependent RNA polymerase activity by the non-structural (NS) 3 helicase and the NS4B membrane protein
Piccininni, S
Varaklioti, A
Nardelli, M
Dave, B
Raney, KD
McCarthy, JEG
[J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (47) : 45670 - 45679
[9] Hepatitis C virus (HCV) NS5A binds RNA-dependent RNA polymerase (RdRP) NS5B and modulates RNA-dependent RNA polymerase activity
Shirota, Y
Luo, H
Qin, WP
Kaneko, S
Yamashita, T
Kobayashi, K
Murakami, S
[J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (13) : 11149 - 11155

← 1 →