Synthesis of carbocyclic aminonucleosides

Daluge, Susan M.; Vince, Robert

doi:10.1021/jo00406a002

Cited by 112 publications

(44 citation statements)

References 6 publications

(10 reference statements)

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“…All carbocyclic nucleosides were from the common intermediate, cis-4-acetamidocyclopent-2-enemethyl acetate, previously described (12). Spectra (infrared, ultraviolet, and proton magnetic resonance), and elemental analysis (C, H, N) are consistent with the structures present in Fig.…”

Section: Methodsmentioning

confidence: 60%

Potent and selective activity of a new carbocyclic nucleoside analog (Carbovir: NSC 614846) against human immunodeficiency virus In vitro

Vince

Mei

Brownell

et al. 1988

Biochemical and Biophysical Research Communications

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224

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Section: Methodsmentioning

confidence: 60%

Potent and selective activity of a new carbocyclic nucleoside analog (Carbovir: NSC 614846) against human immunodeficiency virus In vitro

Vince

Mei

Brownell

et al. 1988

Biochemical and Biophysical Research Communications

Self Cite

224

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“…An (1,22,26). The chemical synthesis of cyclaradine was facilitated through the use of a simple, high-yield route to carbocyclic nucleoside analogs developed by Daluge and Vince (7,8).…”

Section: Discussionmentioning

confidence: 99%

Comparison of the efficacy of vidarabine, its carbocyclic analog (cyclaradine), and cyclaradine-5'-methoxyacetate in the treatment of herpes simplex virus type 1 encephalitis in mice

Shannon¹,

Westbrook²,

Arnett³

et al. 1983

Antimicrob Agents Chemother

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The relative therapeutic effects of vidarabine (9-,-D-arabinofuranosyladenine), cyclaradine (the adenosine deaminase-resistant carbocyclic analog of vidarabine), and cyclaradine-5'-methoxyacetate in the parenteral treatment of systemic herpes simplex virus type 1 infections in Swiss mice were determined. Among control mice inoculated intraperitoneally with virus, a mortality rate of 95% was observed. The intraperitoneal administration of nontoxic doses of vidarabine (125 to 250 mg/kg per day) or cyclaradine (113 to 450 mg/kg per day), by daily injections for 7 days beginning 4 h after virus inoculation, reduced mortality to 0 to 10%, Amnong control animals inoculated intracerebrally with 32 50% lethal doses of virus, 100%to mortality was observed, with a mean survival time of 4.6 days.Treatment with either drug at equimolar dose levels ranging from ca. 32 to 750 mg/kg per day produced significant (P < 0.0005), dose-dependent increases in the mean survival time of animals dying of herpesvirus encephalitis. Mice inoculated intracerebraily with 10 50o lethal doses of virus exhibited 97% mortality and a mean survival time of 5.5 to 6.4 days. Treatment with vidarabine, cyclaradine, or cyclaradine-5'-methoxyacetate significantly increased the mean survival time of dying animals and, at doses ranging from 250 to 750 mg/kg per day, produced significant increases in survival. The three drugs displayed equivalent antiviral efficacy in vivo. Drug toxicity (measured by weight loss) was not detected in mice treated with cyclaradine or cyclaradine-5'-methoxyacetate at 750 mg/kg per day, whereas severe toxicity (weight loss of -3 g) was observed in mice treated with vidarabine at an equivalent dose level. Thus, cyclaradine or its 5'-methoxyacetic acid ester may possess some advantage over vidarabine in the treatment of severe herpesvirus infections and should therefore be considered for clinical trials in humans.

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“…Reduction of the azide and anchimerically assisted hydrolysis of the acetamide group by the cis hydroxyl substituent gave the diamine 70. This compound was converted to 40 and finally to 36a after epimerization at C-2' .27, 29 Shealy and ODell converted exo-bicyclo[2.2.l]hept-5-en-2-ol to racemic mixtures of 4-amino-3-hydroxy and 4-amino-2-hydroxycyclopentanemethanol in the manner described for the carbocyclic ribofuranosylamine 6 (Scheme These amines served respectively as precursors for the carbocyclic analogues of 2'-deoxy and 3'-deoxyadenosine (37a and 38a). Alternatively, these compounds were accessed directly from ( -)-aristeromycin after treatment with acetyl bromide.38 As shown in Scheme IX, bromide attack on the generated acetoxonium ion 75 produced 2' and 3'-bromonucleosides 76 and 77 with inverted configuration.…”

Section: Other Sugar Isosteresmentioning

confidence: 99%