Synthesis, evaluation of anti-HIV-1 and anti-HCV activity of novel 2′,3′-dideoxy-2′,2′-difluoro-4′-azanucleosides

被引：28

作者：

Martinez-Montero, Saul ^{[1
,2
,3
]}

Fernandez, Susana ^{[2
,3
]}

Sanghvi, Yogesh S. ^{[4
]}

Theodorakis, Emmanuel A. ^{[1
]}

Detorio, Mervi A. ^{[5
,6
]}

Mcbrayer, Tamara R. ^{[7
]}

Whitaker, Tony ^{[7
]}

Schinazi, Raymond F. ^{[5
,6
]}

Gotor, Vicente ^{[2
,3
]}

Ferrero, Miguel ^{[2
,3
]}

机构：

[1] Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USA

[2] Univ Oviedo, Dept Quim Organ & Inorgan, E-33006 Oviedo, Asturias, Spain

[3] Univ Oviedo, Inst Univ Biotecnol Asturias, E-33006 Oviedo, Asturias, Spain

[4] Rasayan Inc, Encinitas, CA 92024 USA

[5] Emory Univ, Sch Med, Dept Pediat, Ctr AIDS Res, Decatur, GA 30033 USA

[6] Vet Affairs Med Ctr, Decatur, GA 30033 USA

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

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2012年 / 20卷 / 23期

基金：

美国国家卫生研究院; 美国国家科学基金会;

关键词：

Azanucleosides; Synthesis; Anti-HIV-1; Anti-HCV; L-Pyroglutamic acid; IMMUNODEFICIENCY-VIRUS TYPE-1; STEREOSELECTIVE-SYNTHESIS; OLIGONUCLEOTIDE SYNTHESIS; PYRROLIDINE SUGARS; HIV ACTIVITY; NUCLEOSIDES; DERIVATIVES; ANALOGS; CANCER; AZANUCLEOSIDES;

D O I：

10.1016/j.bmc.2012.09.026

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A series of 2',3'-dideoxy-2',2'-difluoro-4'-azanucleosides of both pyrimidine and purine nucleobases were synthesized in an efficient manner starting from commercially available L-pyroglutamic acid via glycosylation of difluorinated pyrrolidine derivative 15. Several 4'-azanucleosides were prepared as a separable mixture of alpha- and beta-anomers. The 6-chloropurine analogue was obtained as a mixture of N-7 and N-9 regioisomers and their structures were identified based on NOESY and HMBC spectral data. Among the 4'-azanucleosides tested as HIV-1 inhibitors in primary human lymphocytes, four compounds showed modest activity and the 5-fluorouracil analogue (18d) was found to be the most active compound (EC50 = 36.9 mu M) in this series. None of the compounds synthesized in this study demonstrated anti-HCV activity. (C) 2012 Elsevier Ltd. All rights reserved.

引用

页码：6885 / 6893

页数：9

共 54 条

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