Abstract
The attempted synthesis of a ring-expanded guanosine (1) containing the imidazo[4,5-e][1,3]diazepine ring system by condensation of 1-(2'-deoxy-beta-D-erythropentofuranosyl)-4-ethoxycarbonylimidazole-5-carbaldehyde (2) with guanidine resulted in the formation of an unexpected product, 1-(2'-deoxy-beta-D-erythropentofuranosyl)-5-(2, 4-diamino-3, 6-dihydro-1,3, 5-triazin-6-yl)imidazole-4-carboxamide (7). The structure as well as the pathway of formation of 7 was corroborated by isolation of the intermediate, followed by its conversion to the product. Nucleoside 7 showed promising in vitro anti-helicase activity against the West Nile virus NTPase/helicase with an IC50 of 3-10 microg/mL.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Antiviral Agents / chemical synthesis*
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Antiviral Agents / chemistry
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Dose-Response Relationship, Drug
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Guanosine / analogs & derivatives
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Guanosine / chemistry
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Imidazoles / chemical synthesis
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Imidazoles / chemistry*
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Nucleoside-Triphosphatase / antagonists & inhibitors
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Nucleoside-Triphosphatase / chemistry
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RNA Helicases / antagonists & inhibitors*
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RNA Helicases / chemistry
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Viral Proteins / antagonists & inhibitors*
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Viral Proteins / chemistry
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West Nile virus / enzymology*
Substances
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Antiviral Agents
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Imidazoles
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Viral Proteins
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Guanosine
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imidazole
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Nucleoside-Triphosphatase
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RNA Helicases