Synthesis and broad spectrum antiviral evaluation of bis(POM) prodrugs of novel acyclic nucleosides

被引：23

作者：

Hamada, Manabu ^{[1
]}

Roy, Vincent ^{[1
]}

McBrayer, Tamara R. ^{[2
]}

Whitaker, Tony ^{[2
]}

Urbina-Blanco, Cesar ^{[3
]}

Nolan, Steven P. ^{[3
]}

Balzarini, Jan ^{[4
]}

Snoeck, Robert ^{[4
]}

Andrei, Graciela ^{[4
]}

Schinazi, Raymond F. ^{[5
]}

Agrofoglio, Luigi A. ^{[1
]}

机构：

[1] Univ Orleans, CNRS, Inst Chim Organ & Analyt, UMR 7311, F-45067 Orleans, France

[2] LLC, RFS Pharma, Tucker, GA 30084 USA

[3] Univ St Andrews, EaStCHEM, Sch Chem, St Andrews KY16 9ST, Fife, Scotland

[4] Katholieke Univ Leuven, Rega Inst Med Res, B-3000 Louvain, Belgium

[5] Emory Univ, Sch Med, Ctr AIDS Res, Dept Pediat,Lab Biochem Pharmacol, Atlanta, GA 30322 USA

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2013年 / 67卷

关键词：

Nucleosides; Synthesis; Olefin cross metathesis; Antiviral properties; Modified heterocycles; ANALOGS; PHOSPHONATES; NUCLEOTIDE; POTENT; T-705;

D O I：

10.1016/j.ejmech.2013.06.053

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of seventeen hitherto unknown ANP analogs bearing the (E)-but-2-enyl aliphatic side chain and modified heterocyclic base such as cytosine and 5-fluorocytosine, 2-pyrazinecarboxamide, 1,2,4-triazole-3-carboxamide or 4-substituted-1,2,3-triazoles were prepared in a straight approach through an olefin acyclic cross metathesis as key synthetic step. All novel compounds were evaluated for their antiviral activities against a large number of DNA and RNA viruses including herpes simplex virus type 1 and 2, varicella zoster virus, feline herpes virus, human cytomegalovirus, hepatitis C virus (HCV), HIV-1 and HIV-2. Among these molecules, only compound 31 showed activity against human cytomegalovirus in HEL cell cultures with at EC50 of similar to 10 mu M. Compounds 8a, 13, 14, and 24 demonstrated pronounced anti-HCV activity without significant cytotoxicity at 100 mu M. (C) 2013 Elsevier Masson SAS. All rights reserved.

引用

页码：398 / 408

页数：11

共 31 条

[1] 1,2,3-TRIAZOLE-[2',5'-BIS-O-(TERT-BUTYLDIMETHYLSILYL)-BETA-D-RIBOFURANOSYL]-3'-SPIRO-5''-(4''-AMINO-1'',2''-OXATHIOL 2'',2''-DIOXIDE) (TSAO) ANALOGS - SYNTHESIS AND ANTI-HIV-1 ACTIVITY
ALVAREZ, R
VELAZQUEZ, S
SANFELIX, A
AQUARO, S
DECLERCQ, E
PERNO, CF
KARLSSON, A
BALZARINI, J
CAMARASA, MJ
[J]. JOURNAL OF MEDICINAL CHEMISTRY, 1994, 37 (24) : 4185 - 4194
[2] Cu(I)-Catalyzed Huisgen Azide-Alkyne 1,3-Dipolar Cycloaddition Reaction in Nucleoside, Nucleotide, and Oligonucleotide Chemistry
Amblard, Franck
Cho, Jong Hyun
Schinazi, Raymond F.
[J]. CHEMICAL REVIEWS, 2009, 109 (09) : 4207 - 4220
[3] DIFFERENTIAL ANTIHERPESVIRUS AND ANTIRETROVIRUS EFFECTS OF THE (S) AND (R) ENANTIOMERS OF ACYCLIC NUCLEOSIDE PHOSPHONATES - POTENT AND SELECTIVE INVITRO AND INVIVO ANTIRETROVIRUS ACTIVITIES OF (R)-9-(2-PHOSPHONOMETHOXYPROPYL)-2,6-DIAMINOPURINE
BALZARINI, J
HOLY, A
JINDRICH, J
NAESENS, L
SNOECK, R
SCHOLS, D
DECLERCQ, E
[J]. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1993, 37 (02) : 332 - 338
[4] Ruthenium-catalyzed ring-closing metathesis: Recent advances, limitations and opportunities
Conrad, JC
Fogg, DE
[J]. CURRENT ORGANIC CHEMISTRY, 2006, 10 (02) : 185 - 202
[5] Acyclic nucleoside phosphonates: A key class of antiviral drugs
De Clercq, E
Holy, A
[J]. NATURE REVIEWS DRUG DISCOVERY, 2005, 4 (11) : 928 - 940
[6] ACYCLIC NUCLEOSIDE PHOSPHONATES: AN UNFINISHED STORY
De Clercq, Erik
[J]. COLLECTION OF CZECHOSLOVAK CHEMICAL COMMUNICATIONS, 2011, 76 (07) : 829 - 842
[7] A NOVEL SELECTIVE BROAD-SPECTRUM ANTI-DNA VIRUS AGENT
DECLERCQ, E
HOLY, A
ROSENBERG, I
SAKUMA, T
BALZARINI, J
MAUDGAL, PC
[J]. NATURE, 1986, 323 (6087) : 464 - 467
[8] Mechanism of action of T-705 against influenza virus
Furuta, Y
Takahashi, K
Kuno-Maekawa, M
Sangawa, H
Uehara, S
Kozaki, K
Nomura, N
Egawa, H
Shiraki, K
[J]. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2005, 49 (03) : 981 - 986
[9] Cidofovir, a new agent with potent anti-herpesvirus activity
Hitchcock, MJM
Jaffe, HS
Martin, JC
Stagg, RJ
[J]. ANTIVIRAL CHEMISTRY & CHEMOTHERAPY, 1996, 7 (03) : 115 - 127
[10] Holy A., 2005, CURRENT PROTOCOLS NU

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