Nucleosides and nucleotides. 128. (2′S)-2′-deoxy-2′-C-methyl-5-iodouridine (SMIU) as a novel potent anti-herpes virus agent

Awano, Hirokazu; Shuto, Satoshi; Baba, Masanori; Kira, Toshihiko; Shigeta, Shirô; Matsuda, Akira

doi:10.1016/s0960-894x(01)80146-3

Cited by 26 publications

(13 citation statements)

References 14 publications

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“…The viability of virus-infected and mock-infected cells was assessed by the MTT method (Pauwels at al., 1988). In a previous report, anti-HSV-1 activity of s-hatoqenatec SM compounds were examined and 5MBU, SMIC and SMIU were shown to have anti-HSV-1 activity (Awano at al., 1994). Anti-VZV and anti-CMV assays were carried out by the plaque reduction assay.…”

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confidence: 97%

“…The synthesis of the (2'S)-2'-C-methyldeoxy (SM) nucleoside compounds was reported previously (Awano et al, 1994) and the chemical structures of SM compounds as well as 2'-fluoro-S-iodoarabinofuranosylpyrimidine (FIAC and FIAU) are illustrated in Fig. 1.…”

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confidence: 99%

“…This was based on the method of Takeuchi which was reported previously but is only able to assess anti-HSV-1 activity and not anti-HSV-2 activity (Takeuchi at al., 1991;Awano at al., 1994). This was based on the method of Takeuchi which was reported previously but is only able to assess anti-HSV-1 activity and not anti-HSV-2 activity (Takeuchi at al., 1991;Awano at al., 1994).…”

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confidence: 99%

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The FIAU Derivative (2′S)-2′-Deoxy-2′-C-Methyl-5-Iodouridine (SMIU) is a Novel, Less Cytotoxic and Potent anti-HSV and anti-VZV Agent

Kira

Awano

Shuto

et al. 1996

Antivir Chem Chemother

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In this study, the anti-herpetic activities of novel 2'methyl nucleoside analogues which were substituted at the 5 position of the pyrimidine with a halogen were investigated. The 2'-fluoro-5-iodo-aracytosine (FIAC) congeners (2'S)-2'·deoxy-2'-G-methylcytidine which were substituted with Br or I at the 5 position (SMBC or SMIC); and 2'-fluoro-5-iodo-arauridine (FIAU) congeners (2'S)-2'-deoxy-2'-G-methyluridine which were substituted with Br or I at the 5 position (SMBU or SMIU), proved to have potent antiviral activities against herpes simplex virus type-1 (HSV-1) and varicella-zoster virus (VZV) but not against herpes simplex virus type -2 (HSV-2).SMIU has a higher selective index against HSV-1 than FIAU, and both SMIC and SMIU showed higher inhibitory effects against VZV replication than aciclovir. The four effective compounds were not inhibitory to a thymidine kinase (TK)-negative HSV-1 strain, and this result indicates that phosphorylation of the compounds by HSV or VZV -TK is necessary for the activation of these compounds.

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confidence: 97%

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confidence: 99%

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confidence: 99%

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The FIAU Derivative (2′S)-2′-Deoxy-2′-C-Methyl-5-Iodouridine (SMIU) is a Novel, Less Cytotoxic and Potent anti-HSV and anti-VZV Agent

Kira

Awano

Shuto

et al. 1996

Antivir Chem Chemother

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“…Given this possibility, the use of the corresponding N-halosuccinimide was investigated and found to be suitable for the generation of the electrophile (Scheme 3). 11,21 The chlorination reaction was carried out with NCS in DMF at 50 ºC and the bromination was carried out with NBS in DMF at room temperature. These reactions gave yields of 71% and 99%, respective-ly.…”

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confidence: 99%

A Short and Convenient Synthesis of New 1,2-Disubstituted Carbocyclic Nucleoside Analogues of Pyrimidine Based on a Cyclopentene Ring

Gonzalez-Moa¹,

Besada²,

Teijeira³

et al. 2004

Synthesis

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The synthesis of a new series of 1,2-disubstituted carbonucleoside analogues, pyrimidines of general structure I, is reported. These compounds were prepared in good yield from (±)-6-azabicyclo[3.2.0]hept-3-en-7-one (1) via two synthetic routes that involve NaBH 4 -mediated C-N bond cleavage as the key step. The uracil derivative Ia was halogenated with Cl, Br, and I at position 5 by treatment with the corresponding N-halosuccinimide.Nucleoside analogues display a wide range of biological activities and have attracted particular attention as antiviral and antitumor agents. 1-4 The synthesis of new modified nucleosides represents an important and increasingly active area of interest for organic chemists in the search for compounds with improved biological properties. 5,6 Within this area, systems of particular interest include carbocyclic nucleosides and 2¢,3¢-dideoxynucleosides. Carbocyclic nucleosides are compounds in which the furanose oxygen atom of a classical nucleoside is replaced by a methylene group. These compounds possess greater metabolic stability toward the nucleoside phosphorylases and a higher lipophilicity, 7 two properties that are potentially beneficial in terms of increased in vivo half life, oral efficiency and cell wall penetration. 8 On the other hand, a number of 2¢,3¢-dideoxynucleosides are currently the drugs of choice for the treatment of certain viral infections (including AIDS). 9 Indeed, the potent HIV-1 inhibitor carbovir and its prodrug, abacavir, combine the two types of structural modification described above.On the basis of the factors outlined above, and as part of our study of the therapeutic potential of 1,2-disubstituted carbonucleosides (OTCs), 10-12 we describe now the synthesis of (±)-cis-1-(2-hydroxymethyl-4-cyclopentenyl)-2,4-pyrimidinediones of structure I (Schemes 1 and 3). We previously developed another series of pyrimidinebased OTCs in which the pseudosugar is a cyclopentane ring, 11 and in this present study unsaturation has now been incorporated into the 2¢,3¢-position of the carbocycle. 12 Such a structural modification also allows versatility in the functionalization of the ring. 5-Halopyrimidines (Ibd, Scheme 3) are not only of interest for their potential chemotherapeutic properties 13 but also as synthetic intermediates in the formation of new carbon-carbon or carbon-heteroatom bonds. 14 Our usual approach to the synthesis of uracil-based OTCs is to construct the heterocyclic base on an appropriate amino alcohol by reaction with a b-alkoxyacryloyl isocyanate followed by acid-catalyzed cyclization according to published procedures. 15,16 The preparation of the uracil derivative Ia, which is the precursor for the other compounds in the series, employed b-lactam 1 as the starting material. Compound 1 was obtained in 46% yield by a [2 + 2]-cycloaddition between cyclopentadiene and chlorosulfonyl isocyanate, 12 two commercially available compounds, and Ia was subsequently prepared following the two synthetic routes outlined in Scheme 1. The first route represents t...

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“…Iodination of 12 and 9, carried out with iodine in nitric acid and dioxane, 22 gave 71% and 58% yields of 13 and 14, respectively. In the bromination and chlorination reactions, carried out in acetic acid with Nbromosuccinimide and N-chlorosuccinimide, respectively, 23 the yield was hardly affected by the presence of the methylene (Scheme 3).…”

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confidence: 99%

Synthesis of 1,2-Disubstituted Carbocyclic Analogs of Pyrimidine and Purine Nucleosides

Santana¹,

Teijeira²,

Terán³

et al. 2004

Synthesis

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Pyrimidine-and purine-based members of a new class of carbocyclic analogs of nucleosides with 1,2-disubstituted carbocycles were synthesized. For the synthesis of the thymidine analog 3, construction of the base on the amino group of (2-aminocyclopentyl)methanol was more efficient than condensation of the base with a diol. The former strategy was accordingly used to prepare other members of the pyrimidine series, namely uracil and thymine derivatives with a methylene between the base and the carbocycle. The uracil derivatives with and without this methylene were halogenated with Cl, Br and I at uracil position 5. The carbocyclic analogs of purine nucleosides with 2-amino-6-chloro purine and 8-azapurine as bases were also efficiently synthesized by construction of the heterocyclic framework on the primary amino group of the appropriate amino alcohol. The chlorine in position 6 of the base was then replaced in good yields by an amino or hydroxyl group, both of which are present at this position in natural nucleosides.

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Nucleosides and nucleotides. 128. (2′S)-2′-deoxy-2′-C-methyl-5-iodouridine (SMIU) as a novel potent anti-herpes virus agent

Cited by 26 publications

References 14 publications

The FIAU Derivative (2′S)-2′-Deoxy-2′-C-Methyl-5-Iodouridine (SMIU) is a Novel, Less Cytotoxic and Potent anti-HSV and anti-VZV Agent

The FIAU Derivative (2′S)-2′-Deoxy-2′-C-Methyl-5-Iodouridine (SMIU) is a Novel, Less Cytotoxic and Potent anti-HSV and anti-VZV Agent

A Short and Convenient Synthesis of New 1,2-Disubstituted Carbocyclic Nucleoside Analogues of Pyrimidine Based on a Cyclopentene Ring

Synthesis of 1,2-Disubstituted Carbocyclic Analogs of Pyrimidine and Purine Nucleosides

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