Nucleosides with self-complementary hydrogen-bonding motifs: synthesis and base-pairing studies of two nucleosides containing the imidazo[4,5-d]pyridazine ring system.

Abstract:

:Synthesis and base-pairing studies of two 2'-deoxyribonucleosides, containing a common heterocyclic base, 7(4)-amino-5(6)H-imidazo[4,5-d]pyridazin-4(7)one (1 and 2), have been reported. The synthesis was accomplished by base-promoted deoxyribosylation of ethyl 5(4)-cyanoimidazole-4(5)-carboxylate (6), followed by ring-closure with hydrazine hydrate. The 1H NMR-based base-pair studies were conducted using DMF-d7 as a solvent by measuring changes in chemical shifts of the amino, hydrazide, imidazole H-2, and the sugar H-1' protons of the nucleosides with variations in concentrations and temperatures. Large downfield chemical shifts were observed for the NH, NH2, and to a lesser extent for the H-1' protons when the temperature was lowered from 25 to 0 degrees C, and then further down to -50 degrees C in 10 degree intervals. The observed experimental data are consistent with the results of molecular modeling studies. Nucleoside 2 exhibited low level antiviral activity against HIV-1 in CEM-SS cells with an IC50 of 89.2 microM. No cellular toxicity was observed at the highest concentration of the compound tested.

journal_name

Bioorg Med Chem

authors

Ujjinamatada RK,Paulman RL,Ptak RG,Hosmane RS

doi

10.1016/j.bmc.2006.05.043

subject

Has Abstract

pub_date

2006-09-15 00:00:00

pages

6359-67

issue

18

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(06)00417-2

journal_volume

14

pub_type

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