4′-Substituted nucleosides as inhibitors of HIV: an unusual oxetane derivative.

O-Yang, Counde; Kurz, Walter; Eugui, Elsie M.; McRoberts, Mary Jane; Verheyden, Julien P. H.; Kurz, Lilia J.; Walker, K.

doi:10.1016/s0040-4039(00)77668-4

Cited by 98 publications

(35 citation statements)

References 7 publications

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“…Stereoselective reaction with silylated thymine [30] [31] afforded in 75% yield the nucleoside 5, which was heated under reflux in DMF with NaN 3 to give several products of which none was identified. This disappointing result is consistent with another report describing the reaction of 4'-C-[(mesyloxy)methyl]thymidine derivatives with LiN 3 to give the desired 4'-C-(azidomethyl)nucleoside in only low yields [32]. At this point, it was realized that it was impossible to use the mesyloxy group as a leaving group with azide as the nucleophile.…”

supporting

confidence: 85%

See 1 more Smart Citation

Oligonucleotides Containing Novel 4′-C- or 3′-C-(Aminoalkyl)-Branched Thymidines

Pfundheller¹,

Bryld²,

Olsen³

et al. 2000

HCA

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The synthesis of four novel 3′‐C‐branched and 4′‐C‐branched nucleosides and their transformation into the corresponding 3′‐O‐phosphoramidite building blocks for automated oligonucleotide synthesis is reported. The 4′‐C‐branched key intermediate 11 was synthesized by a convergent strategy and converted to its 2′‐O‐methyl and 2′‐deoxy‐2′‐fluoro derivatives, leading to the preparation of novel oligonucleotide analogues containing 4′‐C‐(aminomethyl)‐2′‐O‐methyl monomer X and 4′‐C‐(aminomethyl)‐2′‐deoxy‐2′‐fluoro monomer Y (Schemes 2 and 3). In general, increased binding affinity towards complementary single‐stranded DNA and RNA was obtained with these analogues compared to the unmodified references (Table 1). The presence of monomer X or monomer Y in a 2′‐O‐methyl‐RNA oligonucleotide had a negative effect on the binding affinity of the 2′‐O‐methyl‐RNA oligonucleotide towards DNA and RNA. Starting from the 3′‐C‐allyl derivative 28, 3′‐C‐(3‐aminopropyl)‐protected nucleosides and 3′‐O‐phosphoramidite derivatives were synthesized, leading to novel oligonucleotide analogues containing 3′‐C‐(3‐aminopropyl)thymidine monomer Z or the corresponding 3′‐C‐(3‐aminopropyl)‐2′‐O,5‐dimethyluridine monomer W (Schemes 4 and 5). Incorporation of the 2′‐deoxy monomer Z induced no significant changes in the binding affinity towards DNA but decreased binding affinity towards RNA, while the 2′‐O‐methyl monomer Z induced decreased binding affinity towards DNA as well as RNA complements (Table 2).

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supporting

confidence: 85%

“…FAB-MS: 852 ([M H] ). 3',5'-Di-O-benzyl-3'-C- [3-(phthalimido)propyl]thymidine (32). Through a soln.…”

Section: 2-di-o-acetyl-5-azido-3-o-benzyl-4-c-[(benzyloxy)methyl]-5mentioning

confidence: 99%

Oligonucleotides Containing Novel 4′-C- or 3′-C-(Aminoalkyl)-Branched Thymidines

Pfundheller¹,

Bryld²,

Olsen³

et al. 2000

HCA

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“…While we were working on our project, the anti-HIV activity of several 4'SdNs was reported by the Syntex group [16][17][18][19][20][21][22] and others [23,24]. Therefore, the anti-HIV activities of 4'SdNs that we studied together with those reported by other groups are listed in Table 2.…”

Section: Structure-activity Relationship (Sar) Of 4'sdnsmentioning

confidence: 87%

A New Paradigm for Developing Antiviral Drugs Exemplified by the Development of Supremely High Anti-HIV Active EFdA

Ohrui¹

2014

J Antivir Antiretrovir

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“…Our interest in the title compound 6 was stimulated by the observation of the in vitro anti-HIV activity of 4′ -substituted nucleosides. 16,17 For example, 4′ -hydroxymethylthymidine exhibits good activity against HIV-1. 17 In addition, compound 5 also shows good activity against HIV-1 in MT-4 cells (IC50 0.20 µg/mL).…”

Section: Figurementioning

confidence: 99%

“…16,17 For example, 4′ -hydroxymethylthymidine exhibits good activity against HIV-1. 17 In addition, compound 5 also shows good activity against HIV-1 in MT-4 cells (IC50 0.20 µg/mL). 14 However, to the best of our knowledge, there is no report on the synthesis and anti-HIV evaluation of 4′ -substituted CANs.…”

Section: Figurementioning

confidence: 99%

Synthesis and antiviral evaluation of 2-amino-1,6-dihydro-6-oxo-9-[4-bis(hydroxymethyl) -2-cyclopenten-1-yl]-9H-purine: an analog of the anti-HIV compound Carbovir

Sharma

Nair²

2000

Arkivoc

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A novel carbovir analog, (±)-2-amino-1,6-dihydro-6-oxo-9-[4-bis(hydroxymethyl)-2-cyclopenten-1-yl]-9H-purine, was synthesized starting from the γ-lactam, 2-azabicyclo [2.2.1]hept-5-en-3-one (7). The key intermediate, 1-acetamido-4-bis(hydroxymethyl)cyclopent-2-ene (10), was prepared by the Pfitzner-Moffatt oxidation of the hydroxymethyl group of 8, aldol condensation of the resulting aldehyde, followed by a Cannizzaro reaction. The guanine base was constructed on the amino group of 10. The structures of the target molecule and the intermediates were confirmed by NMR, UV and HRMS data. Anti-HIV evaluation results are reported.

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4′-Substituted nucleosides as inhibitors of HIV: an unusual oxetane derivative.

Cited by 98 publications

References 7 publications

Oligonucleotides Containing Novel 4′-C- or 3′-C-(Aminoalkyl)-Branched Thymidines

Oligonucleotides Containing Novel 4′-C- or 3′-C-(Aminoalkyl)-Branched Thymidines

A New Paradigm for Developing Antiviral Drugs Exemplified by the Development of Supremely High Anti-HIV Active EFdA

Synthesis and antiviral evaluation of 2-amino-1,6-dihydro-6-oxo-9-[4-bis(hydroxymethyl) -2-cyclopenten-1-yl]-9H-purine: an analog of the anti-HIV compound Carbovir

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