Design, Synthesis, and Antiviral Evaluation of Purine-β-lactam and Purine-aminopropanol Hybrids

被引：59

作者：

D'hooghe, Matthias ^{[1
]}

Mollet, Karen ^{[1
]}

De Vreese, Rob ^{[1
]}

Jonckers, Tim H. M. ^{[2
]}

Dams, Gery ^{[2
]}

De Kimpe, Norbert ^{[1
]}

机构：

[1] Univ Ghent, Dept Sustainable Organ Chem & Technol, Fac Biosci Engn, B-9000 Ghent, Belgium

[2] Janssen Infect Dis, Res & Early Dev, B-2340 Beerse, Belgium

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2012年 / 55卷 / 11期

关键词：

STAUDINGER REACTION; BUILDING-BLOCKS; ASYMMETRIC-SYNTHESIS; NUCLEOSIDE CHIMERA; DNA INTERCALATORS; NATURAL-PRODUCTS; ALKYLATION; INHIBITORS; STEREOSELECTIVITY; DERIVATIVES;

D O I：

10.1021/jm300383k

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Purine-beta-lactam chimera were prepared as a novel class of hybrid systems through N-alkylation of 6-benzylamino- or 6-benzyloxypurine with (omega-haloalkyl)-beta-lactams, followed by reductive ring opening of the beta-lactam ring by LiEt3BH to provide an entry into the class of purine-aminopropanol hybrids. Both new types of hybrid systems were assessed for their antiviral activity and cytotoxicity, resulting in the identification of eight purine-beta-lactam hybrids and two purine-aminopropanol hybrids as promising lead structures.

引用

页码：5637 / 5641

页数：5

共 47 条

[1] 2-amino-6-(1,2,4-triazol-4-yl)-purine: a useful intermediate in the synthesis of 9-alkylguanines [J].

Alarcon, K ;

Martelli, A ;

Demeunynck, M ;

Lhomme, J .

TETRAHEDRON LETTERS, 2000, 41 (37) :7211-7215

[2] Stereocontrolled access to orthogonally protected anti,anti-4-aminopiperidine-3,5-diols through chemoselective reduction of enantiopure β-lactam cyanohydrins [J].

Alcaide, Benito ;

Almendros, Pedro ;

Cabrero, Gema ;

Ruiz, M. Pilar .

JOURNAL OF ORGANIC CHEMISTRY, 2007, 72 (21) :7980-7991

[3] β-lactams:: Versatile building blocks for the stereoselective synthesis of non-β-lactam products [J].

Alcaide, Benito ;

Almendros, Pedro ;

Aragoncillo, Cristina .

CHEMICAL REVIEWS, 2007, 107 (11) :4437-4492

[4] (1-PYRENYLMETHYL)AMINO ALCOHOLS, A NEW CLASS OF ANTITUMOR DNA INTERCALATORS - DISCOVERY AND INITIAL AMINE SIDE-CHAIN STRUCTURE ACTIVITY STUDIES [J].

BAIR, KW ;

TUTTLE, RL ;

KNICK, VC ;

CORY, M ;

MCKEE, DD .

JOURNAL OF MEDICINAL CHEMISTRY, 1990, 33 (09) :2385-2393

[5] 2-[(ARYLMETHYL)AMINO]-2-METHYL-1,3-PROPANEDIOL DNA INTERCALATORS - AN EXAMINATION OF THE EFFECTS OF AROMATIC RING VARIATION ON ANTITUMOR-ACTIVITY AND DNA-BINDING [J].

BAIR, KW ;

ANDREWS, CW ;

TUTTLE, RL ;

KNICK, VC ;

CORY, M ;

MCKEE, DD .

JOURNAL OF MEDICINAL CHEMISTRY, 1991, 34 (07) :1983-1990

[6] Improved antiviral activity of the aryloxymethoxyalaninyl phosphoramidate (APA) prodrug of abacavir (ABC) is due to the formation of markedly increased carbovir 5′-triphosphate metabolite levels [J].

Balzarini, J ;

Aquaro, S ;

Hassan-Abdallah, A ;

Daluge, SM ;

Perno, CF ;

McGuigan, C .

FEBS LETTERS, 2004, 573 (1-3) :38-44

[7] An efficient one-pot synthesis of 6-alkoxy-8,9-dialkylpurines via reaction of 5-amino-4-chloro-6-alkylaminopyrimidines with N,N-dimethylalkaneamides and alkoxide ions [J].

Baraldi, PG ;

Broceta, AU ;

de las Infantas, MJP ;

Mochun, JJD ;

Espinosa, A ;

Romagnoli, R .

TETRAHEDRON, 2002, 58 (38) :7607-7611

[8]

Barrow K.D., 1965, TETRAHEDRON LETT, V6, P3325

[9] Synthesis of β-lactam nucleoside chimera via Kinugasa reaction and evaluation of their antibacterial activity [J].

Basak, A ;

Pal, R .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2005, 15 (08) :2015-2018

[10] One-Pot Synthesis of Azanucleosides from Proline Derivatives - Stereoselectivity in Sequential Processes [J].

Boto, Alicia ;

Hernandez, Dacia ;

Hernandez, Rosendo .

EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, 2010, 2010 (20) :3847-3857

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