HCV NS5A replication complex inhibitors. Part 5: Discovery of potent and pan-genotypic glycinamide cap derivatives

被引：15

作者：

Belema, Makonen ^{[1
]}

Nguyen, Van N. ^{[1
]}

St. Laurent, Denis R. ^{[1
]}

Lopez, Omar D. ^{[1
]}

Qiu, Yuping ^{[1
]}

Good, Andrew C. ^{[3
]}

Nower, Peter T. ^{[2
]}

Valera, Lourdes ^{[2
]}

O'Boyle, Donald R., II ^{[2
]}

Sun, Jin-Hua ^{[2
]}

Liu, Mengping ^{[2
]}

Fridell, Robert A. ^{[2
]}

Lemm, Julie A. ^{[2
]}

Gao, Min ^{[2
]}

Knipe, Jay O. ^{[4
]}

Meanwell, Nicholas A. ^{[1
]}

Snyder, Lawrence B. ^{[1
]}

机构：

[1] Bristol Myers Squibb Res & Dev, Dept Med Chem, Wallingford, CT 06492 USA

[2] Bristol Myers Squibb Res & Dev, Dept Virol, Wallingford, CT 06492 USA

[3] Bristol Myers Squibb Res & Dev, Dept Comp Aided Drug Design, Wallingford, CT 06492 USA

[4] Bristol Myers Squibb Res & Dev, Dept Metab & Pharmacokinet, Wallingford, CT 06492 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2013年 / 23卷 / 15期

关键词：

Daclatasvir; HCV; NS5A; Mandelamide X-ray; Pan-genotype HCV replicon inhibition; Phenylglycine; HEPATITIS-C VIRUS; PLUS RIBAVIRIN; THERAPY; DACLATASVIR; ASUNAPREVIR; INFECTION;

D O I：

10.1016/j.bmcl.2013.05.040

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The isoquinolinamide series of HCV NS5A inhibitors exemplified by compounds 2b and 2c provided the first dual genotype-1a/1b (GT-1a/1b) inhibitor class that demonstrated a significant improvement in potency toward GT-1a replicons compared to that of the initial program lead, stilbene 2a. Structure-activity relationship (SAR) studies that uncovered an alternate phenylglycine-based cap series that exhibit further improvements in virology profile, along with some insights into the pharmacophoric elements associated with the GT-1a potency, are described. (C) 2013 Elsevier Ltd. All rights reserved.

引用

页码：4428 / 4435

页数：8

共 50 条

[31] The NS5A Replication Complex Inhibitors: Difference Makers?
Gish, Robert G.
Meanwell, Nicholas A.
CLINICS IN LIVER DISEASE, 2011, 15 (03) : 627 - +
[32] THE PHARMACOKINETICS OF GS-5816, A PAN-GENOTYPIC HCV NS5A INHIBITOR, IN HCV-UNINFECTED SUBJECTS WITH MODERATE AND SEVERE HEPATIC IMPAIRMENT
Mogalian, E.
Mathias, A.
Brainard, D.
McNally, J.
Moorehead, L.
Hernandez, M.
Perry, R.
Curtis, C.
Lawitz, E.
Lasseter, K.
Marbury, T.
JOURNAL OF HEPATOLOGY, 2014, 60 (01) : S317 - S317
[33] Metabolism and Disposition of Pan-Genotypic Inhibitor of Hepatitis C Virus NS5A Ombitasvir in Humans
Shen, Jianwei
Serby, Michael
Surber, Bruce
Lee, Anthony J.
Ma, Junli
Badri, Prajakta
Menon, Rajeev
Kavetskaia, Olga
de Morais, Sonia M.
Sydor, Jens
Fischer, Volker
DRUG METABOLISM AND DISPOSITION, 2016, 44 (08) : 1148 - 1157
[34] IDENTIFICATION AND PROFILE OF POTENT AND SELECTIVE INHIBITORS OF HCV NS5A PROTEIN
Colonno, R.
Benesik, M.
Peng, E.
Huang, N.
Williams, J.
Zhong, M.
Huq, A.
Wobbe, R.
Fathi, R.
Li, L.
JOURNAL OF HEPATOLOGY, 2009, 50 : S318 - S319
[35] GSK2878175, A POTENT NON-NUCLEOSIDE INHIBITOR OF HCV NS5B WITH PAN-GENOTYPIC ACTIVITY
Hamatake, R.
Voitenleitner, C.
Crosby, R.
Walker, J.
Wang, A.
Wright, L.
Shotwell, B.
Leivers, M.
Peat, A.
Hong, Z.
JOURNAL OF HEPATOLOGY, 2014, 60 (01) : S496 - S496
[36] Discovery of fused tricyclic core containing HCV NS5A inhibitors with pan-genotype activity
Yu, Wensheng
Coburn, Craig A.
Yang, De-Yi
Meinke, Peter T.
Wong, Michael
Rosenblum, Stuart B.
Chen, Kevin X.
Njoroge, George F.
Chen, Lei
Dwyer, Michael P.
Jiang, Yueheng
Nair, Anilkumar G.
Selyutin, Oleg
Tong, Ling
Zeng, Qingbei
Zhong, Bin
Ji, Tao
Hu, Bin
Agrawal, Sony
Xia, Ellen
Zhai, Ying
Liu, Rong
Kong, Rong
Ingravallo, Paul
Asante-Appiah, Ernest
Nomeir, Amin
Fells, James
Kozlowski, Joseph A.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2016, 26 (13) : 3158 - 3162
[37] Discovery of thienoimidazole-based HCV NS5A inhibitors. Part 1: C2-Symmetric inhibitors with diyne and biphenyl linkers
Giroux, Simon
Bilimoria, Darius
Cadilhac, Caroline
Cottrell, Kevin M.
Denis, Francois
Dietrich, Evelyne
Ewing, Nigel
Henderson, James A.
L'Heureux, Lucille
Mani, Nagraj
Morris, Mark
Nicolas, Olivier
Reddy, T. Jagadeeswar
Selliah, Subajini
Shawgo, Rebecca S.
Xu, Jinwang
Chauret, Nathalie
Berlioz-Seux, Francoise
Chan, Laval C.
Das, Sanjoy K.
Grillot, Anne-Laure
Bennani, Youssef L.
Maxwell, John P.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2015, 25 (04) : 936 - 939
[38] A pan-genotypic Hepatitis C Virus NS5A amplification method for reliable genotyping and resistance testing
Walker, Andreas
Ennker, Kim Sophie
Kaiser, Rolf
Luebke, Nadine
Timm, Joerg
JOURNAL OF CLINICAL VIROLOGY, 2019, 113 : 8 - 13
[39] Process chemistry development of velpatasvir: A pan-genotypic NS5A inhibitor for the treatment of hepatitis C infection
Sarma, Keshab
Allan, Kevin
Allen, Darin
Axt, Steve
Fu, Wenyi
Fujimori, Shinji
Heumann, Lars
Heumann, Stacey
Huynh, Grace
Keaton, Katie
Lapina, Olga
Levins, Chris
Li, Lei
Macleod, Patricia
Mundal, Devon
Pcion, Dominika
Reddy, P. Ganapati
Rieder, Curtis
Roberts, Ben
Roever, Lyubov
Shah, Nisha
Shi, Bing
Teresk, Martin
Wang, Silas
Wenderski, Todd
Werner, Erik
Wolckenhauer, Scott
Zhang, Michael
ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2016, 252
[40] NOVEL, POTENT, PAN-GENOTYPIC HCV NS3/4A PROTEASE INHIBITORS WITH A HIGH BARRIER TO RESISTANCE
Buckman, B. O.
Kossen, K.
Nicholas, J. B.
Serebryany, V.
Ruhrmund, D.
Rajagopalan, R.
Misialek, S.
Hooi, L.
Aleskovski, N.
Pan, L.
Huang, L.
Schaefer, C. J.
Rajyaguru, S.
Le Pogam, S.
Najera, I.
Klumpp, K.
Seiwert, S.
JOURNAL OF HEPATOLOGY, 2011, 54 : S472 - S472

← 1 2 3 4 5 →