Structure-based design and synthesis of macrocyclic human rhinovirus 3C protease inhibitors

被引：10

作者：

Namoto, Kenji ^{[1
]}

Sirockin, Finton ^{[1
]}

Sellner, Holger ^{[1
]}

Wiesmann, Christian ^{[1
]}

Villard, Frederic ^{[1
]}

Moreau, Robert J. ^{[2
]}

Valeur, Eric ^{[1
,3
]}

Paulding, Stephanie C. ^{[1
]}

Schleeger, Simone ^{[1
]}

Schipp, Kathrin ^{[1
]}

Loup, Joachim ^{[1
]}

Andrews, Lori ^{[2
]}

Swale, Ryann ^{[2
]}

Robinson, Michael ^{[2
]}

Farady, Christopher J. ^{[1
]}

机构：

[1] Novartis Inst BioMed Res, Novartis Campus, CH-4002 Basel, Switzerland

[2] Novartis Inst BioMed Res, 5300 Chiron Way, Emeryville, CA 94608 USA

[3] AstraZeneca, IMED Biotech Unit, Med Chem Cardiovasc & Metab Dis, Gothenburg, Sweden

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2018年 / 28卷 / 05期

关键词：

Rhinovirus 3C protease; Protease inhibition; Covalent inhibitor; Macrocycle; Structure-based drug design; Solid phase synthesis; VITRO ANTIVIRAL ACTIVITY; BIOLOGICAL EVALUATION; DISCOVERY;

D O I：

10.1016/j.bmcl.2018.01.064

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The design and synthesis of macrocyclic inhibitors of human rhinovirus 3C protease is described. A macrocyclic linkage of the P1 and P3 residues, and the subsequent structure-based optimization of the macrocycle conformation and size led to the identification of a potent biochemical inhibitor 10 with sub-micromolar antiviral activity. (C) 2018 Elsevier Ltd. All rights reserved.

引用

页码：906 / 909

页数：4

共 50 条

[41] Design, synthesis and evaluation of 2,2-dimethy1-1,3-dioxolane derivatives as human rhinovirus 3C protease inhibitors
Zhang, Qiyan
Cao, Ruiyuan
Liu, An
Lei, Shihai
Li, Yuexiang
Yang, Jingjing
Li, Song
Xiao, Junhai
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2017, 27 (17) : 4061 - 4065
[42] Design, synthesis, and evaluation of inhibitors of Norwalk virus 3C protease
Tiew, Kok-Chuan
He, Guijia
Aravapalli, Sridhar
Mandadapu, Sivakoteswara Rao
Gunnam, Mallikarjuna Reddy
Alliston, Kevin R.
Lushington, Gerald H.
Kim, Yunjeong
Chang, Kyeong-Ok
Groutas, William C.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2011, 21 (18) : 5315 - 5319
[43] Tripeptide aldehyde inhibitors of human rhinovirus 3C protease:: Design, synthesis, biological evaluation, and cocrystal structure solution of P1 glutamine isosteric replacements
Webber, SE
Okano, K
Little, TL
Reich, SH
Xin, Y
Fuhrman, SA
Matthews, DA
Love, RA
Hendrickson, TF
Patick, AK
Meador, JW
Ferre, RA
Brown, EL
Ford, CE
Binford, SL
Worland, ST
JOURNAL OF MEDICINAL CHEMISTRY, 1998, 41 (15) : 2786 - 2805
[44] Structure-based design of parasitic protease inhibitors
Li, RS
Chen, XW
Gong, BQ
Selzer, PM
Li, Z
Davidson, E
Kurzban, G
Miller, RE
Nuzum, EO
McKerrow, JH
Fletterick, RJ
Gillmor, SA
Craik, CS
Kuntz, ID
Cohen, FE
Kenyon, GL
BIOORGANIC & MEDICINAL CHEMISTRY, 1996, 4 (09) : 1421 - 1427
[45] STRUCTURE-BASED DESIGN OF ASPARTYL PROTEASE INHIBITORS
THAISRIVONGS, S
ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 1995, 209 : 20 - CINF
[46] Azapeptide inhibitors for human rhinovirus 3C proteinase.
Nimkar, SK
Venkatraman, S
Kong, JS
Aube, J
Hanzlik, RP
Wang, QM
ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 1997, 214 : 210 - MEDI
[47] Design of a Human Rhinovirus-14 3C Protease-Inducible Caspase-3
Wagner, Hanna J.
Weber, Wilfried
MOLECULES, 2019, 24 (10)
[48] Structure-based design and synthesis of triazole-based macrocyclic inhibitors of norovirus protease: Structural, biochemical, spectroscopic, and antiviral studies
Weerawarna, Pathum M.
Kim, Yunjeong
Kankanamalage, Anushka C. Galasiti
Damalanka, Vishnu C.
Lushington, Gerald H.
Alliston, Kevin R.
Mehzabeen, Nurjahan
Battaile, Kevin P.
Lovell, Scott
Chang, Kyeong-Ok
Groutas, William C.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2016, 119 : 300 - 318
[49] Design, synthesis, and bioevaluation of viral 3C and 3C-like protease inhibitors
Prior, Allan M.
Kim, Yunjeong
Weerasekara, Sahani
Moroze, Meghan
Alliston, Kevin R.
Uy, Roxanne Adeline Z.
Groutas, William C.
Chang, Kyeong-Ok
Hua, Duy H.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2013, 23 (23) : 6317 - 6320
[50] Conservation of amino acids in human rhinovirus 3C protease correlates with broad-spectrum antiviral activity of rupintrivir, a novel human rhinovirus 3C protease inhibitor
Binford, SL
Maldonado, F
Brothers, MA
Weady, PT
Zalman, LS
Meador, JW
Matthews, DA
Patick, AK
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2005, 49 (02) : 619 - 626

← 1 2 3 4 5 →