A Novel Imidazole Nucleoside Containing a Diaminodihydro-S-triazine as a Substituent: Inhibitory Activity Against the West Nile Virus NTPase/Helicase |
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| Authors: | Ravi K Ujjinamatada Yankanagouda S Agasimundin Peng Zhang Ramachandra S Hosmane Roman Schuessler Peter Borowski |
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| Institution: | 1. Department of Chemistry &2. Biochemistry , Laboratory for Drug Design and Synthesis, University of Maryland, Baltimore County , Baltimore, Maryland, USA;3. Abteilung für Virologie, Bernhard-Nocht-Institut für Tropenmedizin , Hamburg, Germany |
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| Abstract: | The attempted synthesis of a ring-expanded guanosine (1) containing the imidazo4,5-e]1,3]diazepine ring system by condensation of 1-(2′-deoxy-β-D-erythropentofuranosyl)-4-ethoxycarbonylimidazole-5-carbaldehyde (2) with guanidine resulted in the formation of an unexpected product, 1-(2′-deoxy-β-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 IC 50 of 3-10 μg/mL. |
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| Keywords: | Imidazole s-Triazine Nucleoside West Nile Virus Inhibition Rearrangement Ring-expanded nucleoside |
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