A novel imidazole nucleoside containing a diaminodihydro-S-triazine as a substituent: inhibitory activity against the West Nile virus NTPase/helicase.
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.
Ujjinamatada
Ravi K
RK
Laboratory for Drug Design and Synthesis, Department of Chemistry & Biochemistry, University of Maryland, Baltimore County, Baltimore, Maryland 21250, USA.
Agasimundin
Yankanagouda S
YS
Zhang
Peng
P
Hosmane
Ramachandra S
RS
Schuessler
Roman
R
Borowski
Peter
P
Kalicharran
Kishna
K
Fattom
Ali
A
D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D006151:Guanosine / Q000031:analogs & derivatives / Q000737:chemistry; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry*; D043583:Nucleoside-Triphosphatase / Q000037:antagonists & inhibitors / Q000737:chemistry; D020365:RNA Helicases / Q000037:antagonists & inhibitors* / Q000737:chemistry; D014764:Viral Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D014902:West Nile virus / Q000201:enzymology*
D000998:Antiviral Agents; D007093:Imidazoles; D014764:Viral Proteins; D006151:Guanosine; C029899:imidazole; D043583:Nucleoside-Triphosphatase; D020365:RNA Helicases