TY - JOUR
T1 - Carbocyclic Analogues of Xylofuranosylpurine Nucleosides. Synthesis and Antitumor Activity
AU - Vince, Robert
AU - Brownell, Jay
AU - Daluge, Susan
PY - 1984/12
Y1 - 1984/12
N2 - (±)-4α-Amino-2α,3β-dihydroxy-1α-cyclopentanemethanol (6), the carbocyclic analogue of xylofuranosylamine, was synthesized from the previously reported 4α-acetamido-2α,3α:-epoxycyclopentane-1α-methanol. Amine 6 was converted to (±)-4α-[(5-amino-6-chloro-4-pyrimidinyl)amino]-2α,3β-dihydroxy-1α-cyclopentanemethanol (7) by condensation with 5-amino-4,6-dichloropyrimidine. From 7, the carbocyclic analogues of xylofuranosyladenine and xylofuranosyl-8-azaadenine were prepared. In contrast to 9-d-D-xyIofuranosyladenine and its 8-aza analogue, the corresponding carbocyclic nucleosides were resistant to deamination by adenosine deaminase. The carbocyclic 8-aza derivative 10 exhibited significant in vivo antitumor activity which varied according to treatment schedule.
AB - (±)-4α-Amino-2α,3β-dihydroxy-1α-cyclopentanemethanol (6), the carbocyclic analogue of xylofuranosylamine, was synthesized from the previously reported 4α-acetamido-2α,3α:-epoxycyclopentane-1α-methanol. Amine 6 was converted to (±)-4α-[(5-amino-6-chloro-4-pyrimidinyl)amino]-2α,3β-dihydroxy-1α-cyclopentanemethanol (7) by condensation with 5-amino-4,6-dichloropyrimidine. From 7, the carbocyclic analogues of xylofuranosyladenine and xylofuranosyl-8-azaadenine were prepared. In contrast to 9-d-D-xyIofuranosyladenine and its 8-aza analogue, the corresponding carbocyclic nucleosides were resistant to deamination by adenosine deaminase. The carbocyclic 8-aza derivative 10 exhibited significant in vivo antitumor activity which varied according to treatment schedule.
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U2 - 10.1021/jm00376a025
DO - 10.1021/jm00376a025
M3 - Article
C2 - 6481772
AN - SCOPUS:0021144193
SN - 0022-2623
VL - 27
SP - 1358
EP - 1360
JO - Journal of medicinal chemistry
JF - Journal of medicinal chemistry
IS - 10
ER -