Analogs of 8-azainosine

Abstract

A convenient synthesis of 8-azapurine ribonucleosides substituted at the 6 position with thio, alkylthio, alkoxy, amino, and alkylamino groups is described. The reaction of 6-(methylthio)-8-azapurine (1) with 2,3,5-tri-O-acetyl-D-ribofuranosyl chloride in the presence of Linde AW-500 molecular sieve gave a 2:1 mixture of 2 and 3, respectively. This mixture was rearranged by heating with molecular sieve in refluxing toluene to give a 6:1 mixture of 2 and 3. Treatment of 2 or 3 with the appropriate nucleophiles at room temperature gave 6-substituted 8-azapurine ribonucleosides (7-substituted 2- or 3-beta-D-ribofuranosyl-3H-1,2,3-triazolo[4,5-d]pyrimidines) 4-13. The thione 11 rearranges to N-beta-D-ribofuranosyl[1,2,3]thiadiazolo[5,4-d]pyrimidin-7-amine (14) in the solid state or in solution. All of these compounds were cytotoxic to H.Ep. No. 2 cells in culture except the parent base, 8-aza-6-(methylthio)purine (1) and the 8-isomers (3,12, and 13). Three of these compounds-8azaadenosine (4), 8-aza-6-(methylthio)purine ribonucleoside (5), and 8-aza-6-(methoxy)purine ribonucleoside (7)-showed borderline activity in the leukemia L1210 system. The thiadiazolopyrimidine (14) showed activity at three dose levels.

8-Azapurines as isosteric purine fluorescent probes for nucleic acid and enzymatic research

“…10 Table 3 Spectral parameters for neutral and ionic forms of selected 8-azapurine nucleosides. The UV spectral data are compiled from Davoll, 87 Hutzenlaub et al, 88 Elliott and Montgomery, 89,90 The very low acidic pK a value of this compound is analogous to that observed in xanthosine (Kulikowska et al, 52 see Fig. 2), and is a consequence of the fact that the N( 9)-H tautomer is energetically much less favored than N(7)-H in xanthine and N( 8)-H in 8-azaXan.…”

N8-Glycosylated 8-Azapurine and Methylated Purine Nucleobases: Synthesis and Study of Base Pairing Properties

“…8-Aza-8-(β-D-ribofuranos-1-yl)-hypoxanthine 47 (15). The crude product from the previous step (7.02 g) was suspended in a mixture of H 2 O (18 mL) and concd aq NH 3 solution (29%, 36 mL), and resulting mixture was stirred at room temperature for 5 h. Volatiles were removed in vacuo, and the crude product was passed through silica gel column using 5−20% of CH 3 OH in CH 2 Cl 2 as an eluent.…”

“…Analogues of N 8 -glycosylated 8-azapurine nucleosides − demonstrate unexpected pairing properties. They were previously shown to form base pairs with isocytosine , and with 8-substituted (NH 2 , OH) hypoxanthine and guanine bases .…”

Synthesis and biological evaluation of 2-fluoro-8-azaadenosine and related compounds

“…None of the analogues with substituents in the aryl moiety (3 to 13) was more active than 2 in vivo. The geometry about the double bond was important, since the (Z)-4-cinnamylthio derivative (14) was inactive both in vitro and in vivo. The 4-(3-phenylpropynyl)thio and 4-(5-phenyl-2,4-pentadienyl)thio derivatives (15 and 16) were at least as active as 2 in vitro; however, they were less active than 2 in vivo.…”